Skip to main content
SpringerLink
Log in

Clinical Pharmacokinetics of Local Anaesthetics

  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

The introduction of the new long acting local anaesthetics, bupivacaine and etidocaine, has stimulated an expansion of interest in regional anaesthesia, particularly for obstetrical applications and pain therapy.

Systemic toxicity following injection of local anaesthetics occurs albeit infrequently, and tentative correlations have been made between the onset of CNS and cardiovascular effects and circulating drug concentrations in both adults and neonates. Amongst other factors, interpretation of these relationships depends upon blood distribution and plasma binding of the agents, sampling sites and acid-base balance.

The disposition kinetics and placental transfer of the amide type agents have been well characterised. In adults their clearance is almost entirely hepatic but in neonates an increase in the renal component is, in part, a reflection of the immaturity of some of the enzymes responsible for their metabolism. Ester type agents are rapidly hydrolysed by plasma pseudocholin-esterase and this has led to a preference for chloroprocaine in some obstetric procedures.

Major determinants of the systemic absorption of the agents after perineural administration include their physicochemical and vasoactive properties, perfusion and tissue binding at the site of injection and whether or not adrenaline has been added. In respect of blood drug concentrations achieved after various regional anaesthetic procedures, the margin of systemic safety appears to favour bupivacaine and etidocaine compared to shorter acting analogues such as lignocaine and mepivacaine. The time course of local anaesthetic remaining at the site of injection has been calculated following intravenous regional anaesthesia and peridural block. This has allowed prediction of the local and systemic accumulation of the drugs following continued dosage.

Blood concentrations of local anaesthetics after perineural injection are not closely related to age, weight or pregnancy but may be influenced by diseases associated with haemodynamic changes and by other drugs given at or around the time of regional blockade.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abdel-Salam, A.R.; Vonwiller, J.B. and Scott, D.B.: Evaluation of etidocaine in extradural block. British Journal of Anaesthesia 47: 1081–1086 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Adjepon-Yamoah, K.K. and Prescott, L.F.: Ugnocaine metabolism in man. British Journal of Pharmacology 47: 672P–673P (1973).

    Google Scholar 

  • Adriani, J. and Campbell, D.: Fatalities following topical application of local anaesthetics to mucous membranes. Journal of the American Medical Association 162: 1527–1530 (1956).

    Article  CAS  Google Scholar 

  • Akerman, B.: Astrom, A.; Ross, S. and Telc, A.: Studies on the absorption, distribution and metabolism of labelled prilocaine and lidocaine in some animal species. Acta Pharmacologica et Toxicologica 24: 389–403 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Aldrete, J.A.; Nicholson, J.; Sada, T.; Davidson, W. and Garrastasu, G.: Cephalic kinetics of intra-arterially injected lidocaine. Oral Surgery 44: 167–172 (1977).

    Article  CAS  Google Scholar 

  • Aldrete, J.A.; Romo-Salas, F.; Arora, S.; Wilson, R. and Rutherford, R.: Reverse arterial blood flow as a pathway for central nervous system toxic responses following injection of local anaesthetics. Anesthesia and Analgesia; Current Researches 57: 428–433 (1978).

    CAS  Google Scholar 

  • Anderson, K.E.; Gennser, G. and Nilsson, E.: Influence of mepivacaine on isolated human foetal hearts at normal and low pH. Acta Physiologica Scandinavica, Suppl. 353: 34–47 (1970).

    Google Scholar 

  • Appleyard, T.N.; Witt, A.; Atkinson, R.E. and Nicholas, R.D.G.: Bupivacaine carbonate and bupivacaine hydrochloride: a comparison of blood concentrations during epidural blockade for vaginal surgery. British Journal of Anaesthesia 46: 530–533 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Aps, C. and Reynolds, F.: The effect of concentration on vaso-activity of bupivacaine and lignocaine. British Journal of Anaesthesia 48: 1171–1174 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Asling, J.H.; Shnider, S.M.; Margolis, A.J.; Wilkinson, G.R. and Way, E.: Paracervical block in obstetrics. II: Etiology of fetal bradycardia following paracervical block anaesthesia. Am. J. Obstet. Gynecol. 107: 626–634 (1970).

    PubMed  CAS  Google Scholar 

  • Asling, J.H.; Shnider, S.M. and Wilkinson, G.R.: Gas chromatographic determination of mepivacaine in capillary blood. Anesthesiology 31: 458–460 (1969).

    Article  CAS  Google Scholar 

  • Ausinsch, B.; Malagodi, M.H. and Munson, E.S.: Diazepam in the prophylaxis of lignocaine seizures. British Journal of Anaesthesia 48: 309–313 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Beazley, J.M.; Taylor, G. and Reynolds, F.: Placental transfer of bupivacaine after paracervical block. Obstetrics and Gynecology 39: 2–6 (1972).

    PubMed  CAS  Google Scholar 

  • Belfrage, P.; Berlin, A.; Linstedt, M. and Raabe, N.: Plasma levels of bupivacaine following pudendal block in labour. British Journal of Anaesthesia 45: 1067–1069 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Belfrage, P.; Irestedt, L. and Berlin, A.: Concentration of bupivacaine in arterial and venous plasma after epidural anaesthesia in man and after intramuscular administration in dog. Acta Anaesthesiologica Scandinavica 19: 85–88 (1975a).

    Article  PubMed  CAS  Google Scholar 

  • Belfrage, P.; Raabe, N. and Berlin, A.: Lumbar epidural analgesia with bupivacaine in labour. American Journal of Obstetrics and Gynecology 121: 360–365 (1975b).

    PubMed  CAS  Google Scholar 

  • Benowitz, N.: Clinical applications of the pharmacokinetics of lidocaine, in Melmon (Ed) Cardiovascular Drug Therapy, Ch. 7 (F.A. Davis Co., Philadelphia 1975).

    Google Scholar 

  • Benowitz, N.L. and Meister, W.: Clinical pharmacokinetics of lignocaine. Clinical Pharmacokinetics 3: 177–201 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Benowitz, N. and Rowland, M.: Determination of lidocaine in blood and tissues. Anesthesiology 39: 638–641 (1973).

    Article  Google Scholar 

  • Berlin, A.; Persson, B.-A. and Belfrage, P.: Micro method for the determination of bupivacaine in maternal and foetal blood during obstetric analgesia. Journal of Pharmacy and Pharmacology 25: 466–469 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Bertler, A.; Lewis, D.H.; Lofstrom, J.B. and Post, C.: In vivo lung uptake of lidocaine in pigs. Acta Anaesthesiologica Scandinavica 22: 530–536 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Biehl, D.; Shnider, S.M.; Levinson, G. and Callender, K.: Placental transfer of lidocaine: Effects of acidosis. Anesthesiology 48: 409–412 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Blair, M.R.: Cardiovascular pharmacology of local anaesthetics. British Journal of Anaesthesia (Suppl.) 47: 247–252 (1975).

    PubMed  Google Scholar 

  • Blankenbaker, W.L.; DiFazio, C.A. and Berry, F.A.: Lidocaine and its metabolites in the newborn. Anesthesiology 42: 325–330 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Blumer, J.; Strong, J.M. and Atkinson, A.J.: The convulsant potency of lidocaine and its N-dealkylated metabolites. Journal of Pharmacology and Experimental Therapeutics 186: 31–36 (1973).

    PubMed  CAS  Google Scholar 

  • Bonica, J.J.: Regional anaesthesia for surgery, in Bonica (Ed) Regional Anesthesia: Recent Advances and Current Status, pp. 123–139 (F.A. Davis, Philadelphia 1971).

    Google Scholar 

  • Bonica, J.J.; Akamalsu, T.J.; Berges, P.U.; Morikawa, K. and Kennedy, W.: Circulatory effects of peridural block. II: Effects of epinephrine. Anesthesiology 34: 514–522 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Boyes, R.N.: A review of the metabolism of amide local anaesthetic agents. British Journal of Anaesthesia 47: 225–230 (1975).

    PubMed  Google Scholar 

  • Braid, D.P. and Scott, D.B.: The systemic absorption of local analgesic drugs. British Journal of Anaesthesia 37: 394–404 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Braid, D.P. and Scott, D.B.: Dosage of lignocaine in epidural block in relation to toxicity. British Journal of Anaesthesia 38: 596–602 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Bridenbaugh, P.O.: Intercostal nerve blockade for evaluation of local anaesthetic agents. British Journal of Anaesthesia 47: 306–312 (1975).

    PubMed  Google Scholar 

  • Bridenbaugh, P.O.; Tucker, G.T.; Moore, D.C.; Bridenbaugh, L.D. and Thompson, G.E.: Preliminary clinical evaluation of etidocaine (Duranest): A new long-acting local anesthetic agent. Acta Anaesthesiologica Scandinavica 18: 165–171 (1974a).

    Article  PubMed  CAS  Google Scholar 

  • Bridenbaugh, P.O.; Tucker, G.T.; Moore, D.C.; Bridenbaugh, L.D.; Thompson, G.E. and Balfour, R.I.: Role of epinephrine in regional block anesthesia with etidocaine: A double-blind study. Anesthesia and Analgesia; Current Researches 53: 430–435 (1974b).

    CAS  Google Scholar 

  • Brodie, B.B.; Lief, P.A. and Poet, R.: The fate of procaine in man following its intravenous administration and methods for the estimation of procaine and diethylaminoethanol. Journal of Pharmacology and Experimental Therapeutics 94: 359–366 (1948).

    PubMed  CAS  Google Scholar 

  • Bromage, P.R.: Epidural Analgesia (Saunders, Philadelphia 1978).

    Google Scholar 

  • Bromage, P.R. and Gertel, M.: Brachial plexus anesthesia in chronic renal failure. Anesthesiology 36: 488–493 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Bromage, P.R. and Robson, J.G.: Concentrations of lignocaine in the blood after intravenous, intramuscular, epidural and endotracheal administration. Anaesthesia 16: 461–478 (1961).

    Article  PubMed  CAS  Google Scholar 

  • Brown, W.U.; Bell, G.C. and Alper, M.H.: Acidosis, local anesthetics, and the newborn. Obstetrics and Gynecology 48: 27–30 (1976).

    PubMed  Google Scholar 

  • Brown, W.U.; Bell, G.C.; Lurie, A.O.; Weiss, J.B.; Scanlon, J.W. and Alper, M.H.: Newborn blood levels of lidocaine and mepivacaine in the first postnatal day following maternal epidural anesthesia. Anesthesiology 42: 698–707 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Burney, R.G. and DiFazio, C.A.: Hepatic clearance of lidocaine during N2O anesthesia in dogs. Anesthesia and Analgesia: Current Researches 55: 322–325 (1976).

    CAS  Google Scholar 

  • Burney, R.G.; DiFazio, C.A. and Foster, J.H.: Effects of pH on protein binding of lidocaine. Anesthesia and Analgesia: Current Researches 57: 478–480 (1978).

    CAS  Google Scholar 

  • Caldwell, J.; Moffatt, J.R.; Smith, R.L.; Lieberman, A.B.; Cawston, M. and Beard, R.W.: Pharmacokinetics of bupivacaine administered epidurally during childbirth. British Journal of Clinical Pharmacology 3: 956P–957P (1976).

    Google Scholar 

  • Caldwell, J.; Moffatt, J.R.; Smith, R.L.; Lieberman, A.B.; Beard, R.W.; Sneddon, W. and Wilson, B.W.: Determination of bupivacaine in human fetal and neonatal blood samples by gasliquid chromatography mass spectrometry. Biomedical Mass Spectrometry 4: 322–325 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Cannell, H.; Walters, H.; Beckett, A.H. and Saunders, A.: Circulating levels of lignocaine after peri-oral injections. British Dental Journal 138: 87–93 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Chinn, W.M.; Zavala, D.C. and Ambre, J.: Plasma levels of lidocaine following nebulized aerosol administration. Chest 71: 346–348 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Chu, S.S.; Rah, K.H.; Brannan, M.D. and Cohen, J.L.: Plasma concentrations of lidocaine after endotracheal spray. Anesthesia and Analgesia: Current Researches 54: 438–441 (1975).

    CAS  Google Scholar 

  • Cobb, M.E.; Buckley, N.; Hu, M.W.; Miller, J.S.; Singh, P. and Schneider, R.S.: Homogeneous enzyme immunoassay for lidocaine in serum. Clinical Chemistry 23: 1163 (1977).

    Google Scholar 

  • Cooper, L.V.; Stephen, C.W. and Aggett, P.J.A.: Elimination of pethidine and bupivacaine in the newborn. Archives of Disease in Childhood 52: 638–641 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Cousins, M.J.; Augustus, J.A.; Gleason, M.; Morgan, D.J. and Thomas, J.: Epidural block for abdominal surgery: Aspects of clinical pharmacology of etidocaine. Anaesthesia and Intensive Care 6: 105–115 (1978).

    PubMed  CAS  Google Scholar 

  • Covino, B.G. and Vassallo, H.G.: Local Anesthetics — Mechanisms of Action and Clinical Use (Grune and Stratton, New York 1976).

    Google Scholar 

  • Cruikshand, D.P.; Lambe, D.W. and DeBacker, L.J.: Intraperitoneal lidocaine anesthesia for postpartum tubal ligation. Obstetrics and Gynecology 42: 127–130 (1973).

    Google Scholar 

  • Cunningham, N.L. and Kaplan, J.A.: A rapid-onset, long-acting regional anesthetic technique. Anesthesiology 41: 509–511 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Curran, J.; Hamilton, C. and Taylor, T.: Topical analgesia before tracheal intubation. Anaesthesia 30: 765–768 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Dawkins, C.J.M.: An analysis of the complications of extradural and caudal block. Anaesthesia 24: 554–563 (1969).

    Article  PubMed  CAS  Google Scholar 

  • De Jong, R.H.: Local Anesthetics, 2nd Ed (Charles C. Thomas, Springfield, III. 1977).

    Google Scholar 

  • De Jong, R.H. and Heavner, J.E.: Diazepam and lidocaine-in-duced cardiovascular changes. Anesthesiology 39: 633–638 (1973).

    Article  PubMed  Google Scholar 

  • Dhuner, K.G.: Frequency of general side reactions after regional anaesthesia with mepivacaine with and without vasoconstrictors. Acta Anaesthesiologica Scandinavica (Suppl.) 48: 23–43 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Dhuner, K.G.; Harthon, J.G.L.; Herbring, B.G. and Lie, T.: Blood levels of mepivacaine after regional anaethesia. British Journal of Anaesthesia 37: 746–752 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Dhuner, K.G. and Lund, N.: Intercostal blocks with etidocaine. Acta Anaesthesiologica Scandinavica (Suppl.) 60: 39–42 (1975).

    Article  PubMed  CAS  Google Scholar 

  • DuSouich, P. and Erill, P.: Altered metabolism of procainamide and procaine in patients with pulmonary and cardiac diseases. Clinical Pharmacology and Therapeutics 21: 101 (1977).

    Google Scholar 

  • Engberg, G.; Holmdahl, M.H. and Edstrom, H.H.: A comparison of the local anesthetic properties of bupivacaine and two new long-acting agents, HS 37 and etidocaine in epidural analgesia. Acta Anaesthesiologica Scandinavica 18: 277–289 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Englesson, S.: The influence of acid-base changes on central nervous system toxicity of local anaesthetic agents. I. Acta Anaesthesiologica Scandinavica 18: 79–87 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Englesson, S. and Grevsten, S.: The influence of acid-base changes on central nervous system toxicity of local anaesthetic agents. II. Acta Anaesthesiologica Scandinavica 18: 88–103 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Erdemir, H.A.; Soper, L.E. and Sweet, R.E.: Studies of factors affecting peridural anesthesia. Anesthesia and Analgesia: Current Researches 44: 400–404 (1966).

    Google Scholar 

  • Eriksson, E.: Prilocaine. An experimental study in man of a new local anaesthetic with special regards to efficacy, toxicity, and excretion. Acta Chirurgica Scandinavica (Suppl.) 358: 1–82 (1966).

    PubMed  CAS  Google Scholar 

  • Evans, C.J.; Dewar, J.A.; Boyes, R.N. and Scott, D.B.: Residual nerve block following intravenous regional anaesthesia. British Journal of Anaesthesia 46: 668–670 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Finster, M.; Perel, J.M.; Hinsvark, O.N. and O’Brien, J.E.: Reassessment of the metabolism of 2-chloroprocaine hydrochloride (Nesacaine). Abstract, American Society of Anesthetists Meeting, San Francisco (1973).

    Google Scholar 

  • Foldes, F.F.; Molloy, R.; McNall, P.G. and Koukal, L.R.: Comparison of toxicity of intravenously given local anesthetic agents in man. Journal of the American Medical Association 172: 1493–1498 (1960).

    Article  PubMed  CAS  Google Scholar 

  • Foldes, F.F.; Davidson, G.N.; Duncalf, D. and Kuwabarra, S.: The intravenous toxicity of local anesthetic agents in man. Clinical Pharmacology and Therapeutics 6: 328–335 (1965).

    PubMed  CAS  Google Scholar 

  • Freeman, D.W. and Arnold, N.I.: Paracervical block with low doses of chloroprocaine. Journal of the American Medical Association 231: 56 (1975).

    Article  Google Scholar 

  • Fujimori, M.; Kato, M.; Nishimura, K. and Kataoka, T.: LAC-43 (Marcain) in epidural anesthesia and its blood concentrations. Japanese Journal of Anesthesiology 16: 307–312 (1967).

    PubMed  CAS  Google Scholar 

  • Ghoneim, M.M. and Pandya, H.: Plasma proiein binding of bupivacaine and its interaction with other drugs in man. British Journal of Anaesthesia 46: 435–438 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Gibaldi, M. and McNamara, P.J.: Apparent volumes of distribution and drug binding to plasma proteins and tissues. European Journal of Clinical Pharmacology 13: 373–378 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Halkin, H.; Meffin, P.; Melmon, K.L. and Rowland, M.: Influence of congestive heart failure on blood levels of lidocaine and its active monodeethylated metabolite. Clinical Pharmacology and Therapeutics 17: 669–676 (1975).

    PubMed  CAS  Google Scholar 

  • Hollmen, A.; Korhonen, M. and Ojala, A.: Bupivacaine in paracervical block: plasma levels and changes in maternal and foetal acid-base balance. British Journal of Anaesthesia 41: 603–608 (1969a).

    Article  PubMed  CAS  Google Scholar 

  • Hollmen, A.; Ojala, A. and Korhonen, M.: Paracervical block with marcaine/adrenaline. Acta Anaesthesiologica Scandinavica 13: 1–9 (1969b).

    Article  PubMed  CAS  Google Scholar 

  • Hook, R.; Greenberg, R.A. and Hehre, F.W.: Continuous lumbar peridural anesthesia in obstetrics. VII: Distribution of local anesthetic agents in maternal and fetal blood. Anesthesia and Analgesia: Current Researches 50: 693–698 (1971).

    Article  CAS  Google Scholar 

  • Irgens, T.R.; Henderson, W.M. and Shelver, W.H.: GLC analysis of lidocaine in blood using an alkali flame-ionization detector. Journal of Pharmaceutical Sciences 65: 608–610 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Jorfeldt, L.; Lofstrom, B.; Pernow, B.; Persson, B.; Wahren, J. and Widman, B.: The effect of local anaesthetics on the central circulation and respiration in man and dog. Acta Anaesthesiologica Scandinavica 12: 153–169 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Kalow, W.: Hydrolysis of local anesthetics by human serum Cholinesterase. Journal of Pharmacology and Experimental Therapeutics 104: 122–134 (1952).

    PubMed  CAS  Google Scholar 

  • Karlsson, E.; Collste, P. and Rawlins, M.D.: Plasma levels of lidocaine during combined treatment with Phenytoin and procainamide. European Journal of Clinical Pharmacology 7: 455–459 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Karvonen, S.; Jokinen, K.; Karvonen, P. and Hollmen, A.: Arterial and venous blood lidocaine concentrations after local anaesthesia of the respiratory tract using an ultrasonic nebulizer. Acta Anaesthesiologica Scanindavica 20: 156–159 (1976).

    Article  CAS  Google Scholar 

  • Keenaghan, J.B.: The determination of lidocaine and prilocaine in whole blood by gas chromatography. Anesthesiology 29: 110–112 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Keenaghan. J.B. and Boyes, R.N.: The tissue distribution, metabolism and excretion of lidocaine in rats, pigs, dogs and man. Journal of Pharmacology and Experimental Therapeutics 180: 454–463 (1972).

    PubMed  CAS  Google Scholar 

  • Kennedy, W.F.; Everett, G.B.: Cobb, L.A. and Allen, G.D.: Simultaneous systemic and hepatic hemodynamic measurements during high peridural anesthesia in normal men. Anesthesia and Analgesia: Current Researches 50: 1069–1077 (1971).

    Article  CAS  Google Scholar 

  • Lalka, D.; Vicuna, N.; Burrow, S.R.; Jones, D.J.; Ludden, T.M.; Haegele, K.D. and McNay, J.L.: Bupivacaine and other amide local anesthetics inhibit the hydrolysis of chloroprocaine by human serum. Anesthesia and Analgesia: Current Researches 57: 534–539 (1978).

    CAS  Google Scholar 

  • Listen, W.A.; Adjepon-Yamoah, K.K. and Scott, D.B.: Foetal and maternal lignocaine levels after paracervical block. British Journal of Anaesthesia 45: 750–754 (1973).

    Article  Google Scholar 

  • Lofstrom, B. (Ed): Clinical experience with long-acting local anaesthetics. Acta Anaesthesiologica Scandinavica (Suppl.) 60: 1–141 (1975).

    Google Scholar 

  • Lofstrom, J.B.: Tissue distribution of local anesthetics with special reference to the lung. International Anesthesiology Clinics 16: 53–72 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Loo, J.C.K. and Riegelman, S.: New method for calculating the intrinsic absorption rate of drugs. Journal of Pharmaceutical Sciences 57: 918–928 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Lund, P.C.; Bush, D.F. and Covino, B.G.: Determinants of etidocaine concentration in the blood. Anesthesiology 42: 497–503 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Lund, P.C. and Covino, B.G.: Distribution of local anesthetics in man following peridural anesthesia. Journal of Clinical Pharmacology 7: 324–329 (1967).

    CAS  Google Scholar 

  • Lund, P.C. and Cwik, J.C: Citanest A clinical and laboratory study. Anesthesia and Analgesia: Current Researches 44: 623–631 (1965).

    CAS  Google Scholar 

  • Lund, P.C. and Cwik, J.C.: A correlation of the differential penetration and the systemic toxicity of lidocaine, mepivacaine and prilocaine in man. Acta Anaesthesiologica Scandinavica (Suppl.) 23: 475–482 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Lund, P.C.; Cwik, J.C.; Gannon, R.T. and Vassallo, H.G.: Etidocaine for caesarian section — effects on mother and baby. British Journal of Anaesthesia 49: 457–460 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Lund, P.C.; Cwik, J.C. and Pagdanganan, R.T.: Etidocaine: A new long-acting local anesthetic agent. Anesthesia and Analgesia: Current Researches 52: 482–494 (1973).

    CAS  Google Scholar 

  • Magno, R.; Berlin, A.; Karlsson, K. and Kjellmer, I.: Anesthesia for Cesarian section. IV: Placental transfer and neonatal elimination of bupivacaine following epidural analgesia for elective Cesarian section. Acta Anaesthesiologica Scandinavica 20: 141–146 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Malogodi, M.H.; Munson, E.S. and Embro, M.J.: Relation of etidocaine and bupivacaine toxicity to rate of infusion in Rhesus monkeys. British Journal of Anaesthesia 49: 121–125 (1977).

    Article  Google Scholar 

  • Mather, L.E.; Long, G.J. and Thomas, J.: The binding of bupivacaine to maternal and foetal plasma proteins. Journal of Pharmacy and Pharmacology 23: 359–365 (1971a).

    Article  PubMed  CAS  Google Scholar 

  • Mather, L.E.; Long, G.J. and Thomas, J.: The intravenous toxicity and clearance of bupivacaine in man. Clinical Pharmacology and Therapeutics 12: 935–943 (1971b).

    PubMed  CAS  Google Scholar 

  • Mather, L.E. and Thomas, J.: Bupivacaine binding to plasma protein fractions. Journal of Pharmacy and Pharmacology 30: 653–654 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Mather, L.E. and Tucker, G.T.: Meperidine and other basic drugs: General method for their determination in plasma. Journal of Pharmaceutical Sciences 63: 306–307 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Mather, L.E.; Tucker, G.T.; Murphy, T.M.; Stanton-Hicks, M. and Bonica, J.J.: Effect of adding adrenaline to etidocaine and lignocaine in extradural anaesthesia. II: Pharmacokinetics. British Journal of Anaesthesia 48: 989–993 (1976a).

    Article  PubMed  CAS  Google Scholar 

  • Mather, L.E.; Tucker, G.T.; Murphy, T.M.; Stanton-Hicks, M. and Bonica, J.J.: Haemodynamic drug interaction: Peridural lignocaine and intravenous ephedrine. Acta Anaesthesiologica Scandinavica 20: 207–210 (1976b).

    Article  PubMed  CAS  Google Scholar 

  • Mather, L.E.; Tucker, G.T.; Murphy, T.M.; Stanton-Hicks, M. and Bonica, J.J.: Cardiovascular and subjective central nervous system effects of long-acting local anaesthetics in man. Anaesthesia and Intensive Care. In press (1979).

  • Matthes, M. and Schaben, P.: Vergleichende Untersuchungen uber blutspiegel von mepivacain nach resorption aus verscheidenen geweben. Acta Anaesthesiologica Scandinavica (Suppl.) 23: 371–376 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Mazze, R.I. and Dunbar, R.W.: Plasma lidocaine concentrations after caudal, lumbar epidural, axillary block and intravenous regional anesthesia. Anesthesiology 27: 574–579 (1966).

    Article  PubMed  CAS  Google Scholar 

  • McGuiness, G.A.; Merkow, A.J.; Kennedy, R.L. and Erenberg, A.: Epidural anesthesia with bupivacaine for Cesarian section. Anesthesiology 49: 270–273 (1978).

    Article  Google Scholar 

  • Meffin, P.; Long, G.J. and Thomas, J.: Clearance and metabolism of mepivacaine in the human neonate. Clinical Pharmacology and Therapeutics 14: 218–225 (1973).

    PubMed  CAS  Google Scholar 

  • Mihaly, G.W.; Moore, R.G.; Thomas, J.; Triggs, E.J.; Thomas, D. and Shanks, C.H.: The pharmacokinetics of the anilide local anaesthetics in neonates. I: Lignocaine. European Journal of Clinical Pharmacology 13: 143–152 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Moore, D.C.; Bridenbaugh, L.D.; Bridenbaugh, P.O.; Thompson, G.E. and Tucker, G.T.: Does compounding of local anesthetic agents increase their toxicity in humans? Anesthesia and Analgesia: Current Researches 51: 579–585 (1972).

    CAS  Google Scholar 

  • Moore, D.C.; Mather, L.E.; Bridenbaugh, P.O.; Balfour, R.I.; Lysons, D.F. and Horton, W.G.: Arterial and venous plasma levels of bupivacaine following peripheral nerve blocks. Anesthesia and Analgesia: Current Researches 55: 763–768 (1976a).

    CAS  Google Scholar 

  • Moore, D.C.; Mather, L.E.; Bridenbaugh, L.D.; Balfour, R.I.; Lysons, D.F. and Horton, W.G.: Arterial and venous plasma levels of bupivacaine (Marcaine) following epidural and intercostal nerve blocks. Anesthesiology 45: 39–45 (1976b).

    Article  PubMed  CAS  Google Scholar 

  • Moore, R.G.; Thomas, J.; Triggs, E.J.; Thomas, B.D.; Burnard, E.D. and Shanks, C.H.: The pharmacokinetics and metabolism of the anilide local anaesthetics in neonates. III: Mepivacaine. European Journal of Clinical Pharmacology 14: 203–212 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Morgan, D.H.; Cousins, M.J.; McQuillan, D. and Thomas, J.: Disposition and placental transfer of etidocaine in pregnancy. European Journal of Clinical Pharmacology 12: 359–365 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Morgan, D.H.; McQuillan, D. and Thomas, J.: Pharmacokinetics and metabolism of the anilide local anaesthetics in neonates. II: Etidocaine. European Journal of Clinical Pharmacology 13: 365–371 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Morikawa, K.I.; Bonica, J.J.; Tucker, G.T. and Murphy, T.M.: Effects of acute hypovolaemia on lignocaine absorption and cardiovascular response following epidural block in dogs. British Journal of Anaesthesia 46: 631–635 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Morishima, H.O.; Daniel, S.S.; Finser, M.; Poppers, P.J. and James, L.: Transmission of mepivacaine hydrochloride (Carbocaine) across the human placenta. Anesthesiology 27: 147–154 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Munson, E.S.; Martucci, R.W. and Wayman, I.H.: Bupivacaine and lignocaine induced seizures in Rhesus monkeys. British Journal of Anaesthesia 44: 1025–1029 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Munson, E.S.; Paul, W.L. and Embro, J.W.: Central nervous system toxicity of local anesthetic mixtures in monkeys. Anesthesiology 46: 179–183 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Munson, E.S.; Tucker, W.K.; Ausinsch, B. and Malagodi, M.H.: Etidocaine, bupivacaine and lidocaine seizure thresholds in monkeys. Anesthesiology 42: 471–478 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Murphy, T.M.; Mather, L.E.; Zachariah, P. and Bonica, J.J.: Effect of premedication on the hemodynamic and pharmacokinetic response to peridural anesthesia in man. Abstract, American Society for Regional Anesthesia, San Francisco (1977).

    Google Scholar 

  • Nelson, S.D.; Garland, W.A.; Breck, G.D. and Trager, W.F.: Quantification of lidocaine and several metabolites utilizing chemical-ionization mass spectrometry and stable isotope labelling. Journal of Pharmaceutical Sciences 66: 1180–1190 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Patterson, J.R.; Blaschke, T.F.; Hunt, K.K. and Meffin, P.J.: Lidocaine blood concentrations during fiberoptic bronchoscopy. American Review of Respiratory Disease 112: 53–57 (1975).

    PubMed  CAS  Google Scholar 

  • Pelton, D.A.; Daly, M.; Cooper, P.D. and Conn, A.W.: Plasma lidocaine concentrations following topical aerosol application to the trachea and bronchi. Canadian Anaesthetists’ Society Journal 17: 250–255 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Petrie, R.H.; Paul, W.L.; Miller, F.C.; Arca, J.J.; Paul, R.H.; Nakamura, R.M. and Hon, E.H.: Placental transfer of lidocaine following paracervical block. American Journal of Obstetrics and Gynecology 120: 791–801 (1974).

    PubMed  CAS  Google Scholar 

  • Quimby, C.W. Jr.: Influence of blood loss on the duration of regional anesthesia. Anesthesia and Analgesia: Current Researches 44: 387–390 (1965).

    Google Scholar 

  • Raj, P.P.; Rosenblatt, R.; Miller, J.; Katz, R.L. and Carden, E.: Dynamics of local anesthetic compounds in regional anesthesia. Anesthesia and Analgesia: Current Researches 56: 110–117 (1977).

    CAS  Google Scholar 

  • Ralston, D.H. and Shnider, S.M.: The fetal and neonatal effects of regional anesthesia in obstetrics. Anesthesiology 48: 34–64 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Reidenberg, M.M.; James, M. and Dring, L.G.: The rate of procaine hydrolysis in serum of normal subjects and diseased patients. Clinical Pharmacology and Therapeutics 13: 279–284 (1972).

    PubMed  CAS  Google Scholar 

  • Reynolds, F.: Metabolism and excretion of bupivacaine in man: A comparison with mepivacaine. British Journal of Anaesthesia 43: 33–36 (1971a).

    Article  PubMed  CAS  Google Scholar 

  • Reynolds, F.: A comparison of the potential toxicity of bupivacaine, lignocaine and mepivacaine during epidural blockade for surgery. British Journal of Anaesthesia 43: 567–571 (1971b).

    Article  PubMed  CAS  Google Scholar 

  • Rowland, M.: Local anesthetic absorption, distribution and elimination, in E. Eger II (Ed) Anesthetic Uptake and Action pp.332–360 (Williams and Wilkins, Baltimore 1974).

    Google Scholar 

  • Rowland, M.; Thomson, P.D.; Guichard, A. and Melmon, K.L.: Disposition kinetics of lidocaine in normal subjects. Annals of the New York Academy of Sciences 179: 383–398 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Scanlon, J.W.; Brown, W.U.; Weiss, J.B. and Alper, M.H.: Neurobehavioural responses of newborn infants after maternal epidural anesthesia. Anesthesiology 40: 121–128 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Scanlon, J.W.; Ostheimer, G.W.; Lurie, A.O.; Brown, W.V.; Weiss, J.B. and Alper, M.H.: Neurobehavioural responses and drug concentration in newborns after maternal epidural anesthesia with bupivacaine. Anesthesiology 45: 400–405 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Schwartz, M.L.; Covino, B.G.; Narang, R.M.; Sethi, V.; Tholpady, S.S.; Kuangparichat, M.; Giordano, C. and Meyer, M.B.: Blood levels of lidocaine following subcutaneous administration prior to cardiac catheterization. American Heart Journal 88: 721–723 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Scott, D.B.: Evaluation of the toxicity of local anaesthetic agents in man. British Journal of Anaesthesia 47: 56–60 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Scott, D.B.; Jebsen, P.J.R.; Braid, D.P.; Ortengren, B. and Frisch, P.: Factors affecting plasma levels of lignocaine and prilocaine. British Journal of Anaesthesia 44: 1040–1048 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Scott, D.B.; Jebson, P.J.R. and Boyes, R.N.: Pharmacokinetic study of the local anaesthetics bupivacaine (Marcaine) and etidocaine (Duranest) in man. British Journal of Anaesthesia 45: 1010–1012 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Scott, D.B.; Littlewood, D.G.; Covino, G.B. and Drummond, G.B.: Plasma lignocaine concentrations following endotracheal spraying with an aerosol. British Journal of Anaesthesia 48: 899–901 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Shnider, S.M. and Way, E.L.: Plasma levels of lidocaine (Xylocaine) in mother and newborn following obstetrical conduction anesthesia: Clinical applications. Anesthesiology 25: 951–958 (1968).

    Article  Google Scholar 

  • Sjostrand, U. and Widman, B.: Distribution of bupivacaine in the rabbit under normal and acidotic conditions. Acta Anaesthesiologica Scandinavica 50: 1–24 (1973).

    PubMed  CAS  Google Scholar 

  • Smith, R.B.: Uptake of lidocaine from the trachea. Anesthesiology 44: 269 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Smith, R.H.; Brewster, M.A.; MacDonald, J.A. and Thompson, D.S.: Measurement of chloroprocaine and procaine in plasma by flame ionization gas-liquid chromatography. Clinical Chemistry 24: 1599–1602 (1978).

    PubMed  CAS  Google Scholar 

  • Stanton-Hicks, M.d’A.; Berges, P.U. and Bonica, J.J.: Circulatory effect of peridural block. IV: Comparison of the effects of epinephrine and phenylephrine. Anesthesiology 39: 308–314 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Stanton-Hicks, M.; Murphy, T.M.; Bonica, J.J.; Mather, L.E. and Tucker, G.T.: Effects of extradural block: Comparison of the properties, circulatory effects and pharmacokinetics of etidocaine and bupivacaine. British Journal of Anaesthesia 48: 575–586 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Steffenson, J.L.; Shnider, S.M. and DeLorimer, A.A.: Transarterial diffusion of mepivacaine. Anesthesiology 32: 459–460 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Strong, J.M.; Parker, M. and Atkinson, A.J.: Identification of glycinexylidine in patients treated with intravenous lidocaine. Clinical Pharmacology and Therapeutics 14: 67–72 (1973).

    PubMed  CAS  Google Scholar 

  • Teramo, K. and Rajamaki, A.: Foetal and maternal plasma levels of mepivacaine and foetal acid-base balance and heart rate after pericervical block during labour. British Journal of Anaesthesia 43: 300–311 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Thomas, J.; Long, G. and Mather, L.E.: Plasma lignocaine concentrations following topical aerosol application. British Journal of Anaesthesia 41: 442–446 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Thomas, J.; Long, G.; Moore, G.; and Morgan, D.: Plasma protein binding and placental transfer of bupivacaine. Clinical Pharmacology and Therapeutics 19: 426–434 (1976a).

    PubMed  CAS  Google Scholar 

  • Thomas, J. and Meffin, P.: Aromatic hydroxylation of lidocaine and mepivacaine in rats and humans. Journal of Medicinal Chemistry 15: 1046–1049 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Thomas, J.; Morgan, D. and Vine, J.: Metabolism of etidocaine in man. Xenobiotica 6: 39–48 (1976b).

    Article  PubMed  CAS  Google Scholar 

  • Tronick, E.; Wise, S. and Als, H.: Regional obstetric anesthesia and newborn behaviour: Effects over the first ten days of life. Pediatrics 58: 94–100 (1976).

    PubMed  CAS  Google Scholar 

  • Tucker, G.T.: Determination of bupivacaine (Marcaine) and other anilide-type local anesthetics in human blood and plasma by gas chromatography. Anesthesiology 32: 255–260 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Tucker, G.T.: Plasma binding and disposition of local anesthetics. International Anesthesiology Clinics 13: 33–59 (1975a).

    Article  PubMed  CAS  Google Scholar 

  • Tucker, G.T.: Biotransformation and toxicity of local anaesthetics. Acta Anaesthesiologica Belgica (Suppl.) 26: 123–140 (1975b).

    Google Scholar 

  • Tucker, G.T. and Boas, R.A.: Pharmacokinetic aspects of intravenous regional anesthesia. Anesthesiology 34: 538–549 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Tucker, G.T.; Boyes, R.N.; Bridenbaugh, P.O. and Moore, D.C.: Binding of anilide-type local anesthetics in human plasma. I: Relationships between binding, physicochemical properties and anesthetic activity. Anesthesiology 33: 287–303 (1970a).

    Article  PubMed  CAS  Google Scholar 

  • Tucker, G.T.; Boyes, R.N.; Bridenbaugh, P.O. and Moore, D.C.: Binding of anilide-type local anesthetics in human plasma. II: Implications in vitro with special reference to transplacental disposition. Anesthesiology 33: 304–314 (1970b).

    Article  PubMed  CAS  Google Scholar 

  • Tucker, G.T.; Cooper, S.; Littlewood, D.; Buckley, S.P.; Covino, B.G. and Scott, D.B.: Observed and predicted accumulation of local anaesthetic agent during continuous extradural analgesia. British Journal of Anaesthesia 49: 237–242 (1977b).

    Article  PubMed  CAS  Google Scholar 

  • Tucker, G.T. and Mather, L.E.: Pharmacokinetics of local anaesthetic agents. British Journal of Anaesthesia 47: 213–224 (1975a).

    Article  PubMed  Google Scholar 

  • Tucker, G.T. and Mather, L.E.: Plasma protein binding of bupivacaine and its interaction with other drugs in man. British Journal of Anaesthesia 47: 1029–1030 (1975b).

    Article  PubMed  CAS  Google Scholar 

  • Tucker, G.T.; Moore, D.C.; Bridenbaugh, P.O.; Bridenbaugh, L.D. and Thompson, G.E.: Systemic absorption of mepivacaine in commonly used regional block procedures. Anesthesiology 37: 277–287 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Tucker, G.T.; Wiklund, L.; Berlin-Wahlen, A. and Mather, L.E.: Hepatic clearance of local anaesthetics in man. Journal of Pharmacokinetics and Biopharmaceutics 51: 111–122 (1977a).

    Google Scholar 

  • Tucker, G.T. and Mather, L.E.: Absorption and disposition of local anesthetics, in Cousins and Bridenbaugh (Eds) Neural Blockade in Clinical Anesthesia and Management of Pain (Lippincott, New York, 1979).

    Google Scholar 

  • Usubiaga, J.E.; Wikinski, F.A.; Ferrero, R.; Usubiaga, L.E. and Wikinski, R.: Local anesthetic induced convulsions in man: An electroencephalographic study. Anesthesia and Analgesia: Current Researches 45: 611–620 (1966).

    CAS  Google Scholar 

  • Verrill, P.J.: Adverse reactions to local anaesthetics and vasoconstrictor drugs. Practitioner 214: 380–387 (1975).

    PubMed  CAS  Google Scholar 

  • Viegas, O. and Stoelting, R.K.: Lignocaine in arterial blood after laryngotracheal administration. Anesthesiology 43: 491–493 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Wilkund, L.: Human hepatic blood flow and its relation to systemic circulation during intravenous infusion of bupivacaine or etidocaine. Acta Anaesthesiologica Scandinavica 21: 189–199 (1977a).

    Article  Google Scholar 

  • Wilkund, L.: Human hepatic blood flow and its relation to systemic circulation during intravenous infusion of lidocaine. Acta Anaesthesiologica Scandinavica 21: 148–160 (1977b).

    Article  Google Scholar 

  • Wilkund, L. and Berlin-Wahlen, A.: Splanchnic elimination and systemic toxicity of bupivacaine and etidocaine in man. Acta Anaesthesiologica Scandinavica 21: 521–528 (1977).

    Article  Google Scholar 

  • Wilkund, L.; Tucker, G.T. and Engberg, G.: Influence of intravenously administered epinephrine on splanchnic haemodynamics and clearance of lidocaine. Acta Anaesthesiologica Scandinavica 21: 275–281 (1977).

    Article  Google Scholar 

  • Wildsmith, J.A.W.; Tucker, G.T.; Cooper, S.; Scott, D.B. and Covino, B.G.: Plasma concentrations of local anaesthetics after interscalene brachial plexus block. British Journal of Anaesthesia 49: 461–466 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Wilkinson, G.R. and Lund, P.C.: Bupivacaine levels in plasma and cerebrospinal fluid following peridural administration. Anesthesiology 33: 482–486 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Willdeck-Lund, G. and Edstrom, H.: Etidocaine in intercostal nerve block for pain relief after thoracotomy: A comparison with bupivacaine. Acta Anaesthesiologica Scandinavica (Suppl.) 60: 33–38 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Wylie, W.D. and Churchill-Davidson, H.C.; A Practice of Anaesthesia, pp.860–865 (Year Book Medical Publishers, Chicago 1972).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Therapeutics, University of Sheffield, Hallamshire Hospital, Sheffield, S102JF, UK

    G. T. Tucker

  2. Department of Anaesthesia and Intensive Care, Flinders Medical Centre, Flinders University of South Australia, Bedford Park, South Australia, 5042, Australia

    L. E. Mather

Authors
  1. G. T. Tucker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. E. Mather
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This paper is dedicated to Professor John J. Bonica on the occasion of his retirement as Chairman, Department of Anesthesiology, University of Washington, Without him, regional anaesthesia surely would have progressed but not nearly so effectively.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tucker, G.T., Mather, L.E. Clinical Pharmacokinetics of Local Anaesthetics. Clin Pharmacokinet 4, 241–278 (1979). https://doi.org/10.2165/00003088-197904040-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-197904040-00001

Keywords

Search

Navigation