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Cefpirome Clinical Pharmacokinetics

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  • Drug Disposition
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Summary

Cefpirome is a new cephalosporin that exhibits similar in vitro potency to ceftazidime against Gram-negative organisms but has significantly greater in vitro potency against Gram-positive organisms. Cefpirome differs from cefotaxime in that a 3′-pyridinium moiety replaces the acetoxy moiety of cefotaxime. This structural change imparts greater β-lactamase stability, increases the ability to penetrate the outer membrane of Gram-negative bacteria, and enhances activity against Gram-positive organisms.

The pharmacokinetic properties of cefpirome are typical of cephalosporins. The drug can be administered by intravenous or intramuscular injection, but is not well absorbed after oral administration. Bioavailability following intramuscular injection exceeds 90%. Cefpirome exhibits low protein binding (≈10%) and has a volume of distribution similar to extracellular fluid volume.

Cefpirome penetrates the prostate gland, lung, blister fluid, cerebrospinal fluid and peritoneal fluid, reaching concentrations that are similar to those achieved by other later generation cephalosporins. Approximately 80% of an intravenous dose is eliminated unchanged in the urine. No active metabolites of cefpirome have been identified. The elimination half-life of cefpirome is approximately 2 hours. Elimination appears to be primarily by glomerular filtration since the total clearance of cefpirome is approximately equal to creatinine clearance.

The time during which drug concentrations exceed the minimum inhibitory concentration (MIC) represents the most clinically important pharmacodynamic parameter for β-lactam agents. When cefpirome is administered at a dosage of 2g every 12 hours to patients without renal insufficiency [creatinine clearance 70 ml/min (4.2 L/h)], drug concentrations continuously remain above the MIC for pathogens with MIC values of ⩽2 µg/ml. With this dosage regimen, drug concentrations will be above the MIC for a pathogen with an MIC of 4 µg/ml for 80% of the dosage interval. The time above MIC for pathogens with an MIC of 8 µg/ml is only 60% of the dosage interval.

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References

  • Badian M, Malerczyk V, Collins JD, Dixon GT, Verho M, et al. Safety, tolerance and pharmacokinetics of 2.0g cefpirome (HR 810) after single and multiple dosing. Chemotherapy 34: 367–373, 1988

    Article  PubMed  CAS  Google Scholar 

  • Baldwin DR, Maxwell SJR, Honeybourne D, Andrews JM, Ashby JP, et al. The penetration of cefpirome into the potential sites of pulmonary infection. Journal of Antimicrobial Chemotherapy 28: 79–86, 1991

    Article  PubMed  CAS  Google Scholar 

  • Barza M. Principles of tissue penetration of antibiotics. Journal of Antimicrobial Chemotherapy 8 (Suppl. C): 7–28, 1981

    PubMed  CAS  Google Scholar 

  • Barza M, Cuchural G. The penetration of antibiotics into the prostate in chronic bacterial prostatitis. European Journal of Clinical Microbiology 3: 503–505, 1984

    Article  PubMed  CAS  Google Scholar 

  • Brown RF, Kinnick MD, Morin JM, Vasileff RT, Counter FT, et al. Synthesis and biologic evaluation of a series of parenteral 3′-quaternary ammonium cephalosporins. Journal of Medicinal Chemistry 33: 2114–2121, 1990

    Article  PubMed  CAS  Google Scholar 

  • Christ W. Pharmacological properties of cephalosporins. Infection 19 (Suppl. 5): s244–s252, 1991

    Article  PubMed  CAS  Google Scholar 

  • Craig WA, Ebert SC. Continuous infusion of β-lactam antibiotics. Antimicrobial Agents and Chemotherapy 36: 2577–2583, 1992

    Article  PubMed  CAS  Google Scholar 

  • Cunha BA. Antibiotic pharmacokinetic considerations in pulmonary infections. Seminars in Respiratory Infections 6: 168–182, 1991

    PubMed  CAS  Google Scholar 

  • Eng RHK, Cherubin CE, Smith SM, Buccini F, Harris R. In-vitro and in-vivo activity of cefpirome (HR 810) against methicillin-susceptible and -resistant Staphylococcus aureus and Streptococcus faecalis. Journal of Antimicrobial Chemotherapy 23: 373–381, 1989

    Article  PubMed  CAS  Google Scholar 

  • Fair WR, Cordonnier JJ. The pH of prostatic fluid: a reappraisal and therapeutic implications. Journal of Urology 120: 695–698, 1978

    PubMed  CAS  Google Scholar 

  • Gargalianos P, Oppenheim BA, Skepastianos P, Livermore DM, Williams RJ. Activity of cefpirome (HR 810) against Pseudomonas aeruginosa strains with characterized resistance mechanisms to β-lactam antibiotics. Journal of Antimicrobial Chemotherapy 22: 841–848, 1988

    Article  PubMed  CAS  Google Scholar 

  • Goldstein EJC, Citron DM. Comparative in vitro inhibitory and killing activity of cefpirome, ceftazidime, and cefotaxime against Pseudomonas aeruginosa, enterococci, Staphylococcus epidermidis, and methicillin-susceptible and -resistant and tolerant and non-tolerant Staphylococcus aureus. Antimicrobial Agents and Chemotherapy 28: 160–162, 1985

    Article  PubMed  CAS  Google Scholar 

  • Grötsch H, Hajdú P. Interference by the new antibiotic cefpirome and other cephalosporins in clinical laboratory tests, with special regard to the ‘Joffe’ reaction. Journal of Clinical Chemistry and Clinical Biochemistry 25: 49–52, 1987

    Google Scholar 

  • Hancock REW, Bellido F. Factors involved in the enhanced efficacy against gram-negative bacteria of fourth generation cephalosporins. Journal of Antimicrobial Chemotherapy 29 (Suppl. A): 1–6, 1992

    PubMed  CAS  Google Scholar 

  • Jones RN, Pfaller MA, Allen SD, Gerlach EH, Fuchs PC, et al. Antimicrobial activity of cefpirome an update compared to five third-generation cephalosporins against nearly 6000 recent clinical isolates from five medical centers. Diagnostic Microbiology and Infectious Diseases 14: 361–364, 1991

    Article  CAS  Google Scholar 

  • Kavi J, Andrews JM, Ashby JP, Hillman G, Wise R. Pharmacokinetics and tissue penetration of cefpirome, a new cephalosporin. Journal of Antimicrobial Chemotherapy 22: 911–916, 1988

    Article  PubMed  CAS  Google Scholar 

  • Kavi J, Ashby JP, Wise R, Donovan IA. Intraperitoneal penetration of cefpirome. European Journal of Clinical Microbiology and Infectious Diseases 8: 556–558, 1989

    Article  CAS  Google Scholar 

  • Kearns GL, Johnson VA, Hendry IR, Wells TG. Microanalytical high-performance liquid Chromatographic assay for cefpirome in human milk and urine. Journal of Chromatography 574: 356–360, 1992

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi S, Arai S, Hayashi S, Fujimoto K. β-lactamase stability of cefpirome (HR-810), a new cephalosporin with a broad antimicrobial spectrum. Antimicrobial Agents and Chemotherapy 30: 713–718, 1986

    Article  PubMed  CAS  Google Scholar 

  • Lameire N, Malerczyk V, Drees B, Lehr K, Rosenkranz B. Single dose pharmacokinetics of cefpirome in patients with renal impairment. Clinical Pharmacology and Therapeutics 52: 24–30, 1992

    Article  PubMed  CAS  Google Scholar 

  • Lameire NH, Rosenkranz B, Malerczyk V. Influence of renal functional impairment and haemodialysis on the pharmacokinetics of cefpirome. Programs and abstracts of the Twenty-ninth Interscience Conference on Antimicrobial Agents and Chemotherapy, pp. 308, Houston, September 17–20, 1989

  • Lassman HB, Hubbard JW, Chen B, Puri SK. Lack of interaction between cefpirome and alcohol. Journal of Antimicrobial Chemotherapy 29 (Suppl. A): 47–50, 1992

    PubMed  CAS  Google Scholar 

  • Lattrell R, Blumbach J, Duerckheimer W, Fehlhaber H, Fleischmann K, et al. Synthesis and structure-activity relationships in the cefpirome series I. Journal of Antibiotics 41: 1374–1394, 1988

    Article  PubMed  CAS  Google Scholar 

  • Lattrell R, Durckheimer W, Klesel N, Kirrstetter R, Seibert G, et al. HR 810, a new parenteral cephalosporin. Proceedings of the 13th International Congress of Chemotherapy, pp. 99/1–99/4, Vienna, August 28-September 2, 1983

  • Maass L, Malerczyk V, Verho M. Pharmacokinetics of cefpirome (HR 810), a new cephalosporin derivative administered intramuscularly and intravenously to healthy volunteers. Infection 15: 207–210, 1987a

    Article  PubMed  CAS  Google Scholar 

  • Maass L, Malerczyk V, Verho M, Hajdú P, Seeger K, et al. Dose linearity testing of intravenous cefpirome (HR 810), a novel cephalosporin derivate. Infection 15: 202–206, 1987b

    Article  PubMed  CAS  Google Scholar 

  • Malerczyk V, Maass L, Verho M, Hajdú P, Kiesel N, et al. Single and multiple dose pharmacokinetics of intravenous cefpirome (HR 810), a novel cephalosporin derivative. Infection 15: 211–214, 1987

    Article  PubMed  CAS  Google Scholar 

  • Meyer BH, Muller FO, Luus HG, Drees B, Röthig HJ, et al. Safety, tolerance and pharmacokinetics of cefpirome administered intramuscularly to healthy subjects. Journal of Antimicrobial Chemotherapy 29 (Suppl. A): 63–70, 1992

    PubMed  CAS  Google Scholar 

  • Murdoch MB, Peterson LR. Antimicrobial penetration into polymorphonuclear leukocytes and alveolar macrophages. Seminars in Respiratory Infections 6: 112–121, 1991

    PubMed  CAS  Google Scholar 

  • Nakayama I, Akieda Y, Yamaji E, Nitta Y, Ohishi M, et al. Single-and multiple-dose pharmacokinetics of intravenous cefpirome (HR 810) to healthy volunteers. Journal of Clinical Pharmacology 32: 256–266, 1992

    PubMed  CAS  Google Scholar 

  • Nikaido H, Liu W, Rosenberg U. Outer membrane permeability and β-lactamase stability of dipolar ionic cephalosporins containing methoxyamino substituents. Antimicrobial Agents and Chemotherapy 34: 337–342, 1990

    Article  PubMed  CAS  Google Scholar 

  • Nix DE, Goodwin SD, Peloquin CA, Rotella DL, Schentag JJ. Antibiotic tissue penetration and its relevance: models of tissue penetration and their meaning. Antimicrobial Agents and Chemotherapy 35: 1947–1952, 1991a

    Article  PubMed  CAS  Google Scholar 

  • Nix DE, Goodwin SD, Peloquin CA, Rotella DL, Schentag JJ. Antibiotic tissue penetration and its relevance: impact of tissue penetration on infection response. Antimicrobial Agents and Chemotherapy 35: 1953–1959, 1991b

    Article  PubMed  CAS  Google Scholar 

  • Nix DE, Wilton JH, Velasquez N, Budny JL, Lassman HB, et al. Cerebrospinal fluid penetration of cefpirome in patients with non-inflamed meninges. Journal of Antimicrobial Chemotherapy 29 (Suppl. A): 51–57, 1992

    PubMed  Google Scholar 

  • Paradis D, Vallée F, Allard S, Bisson C, Daviau N, et al. Comparative study of pharmacokinetics and serum bactericidal activities of cefpirome, ceftazidime, ceftriaxone, imipenem, and ciprofloxacin. Antimicrobial Agents and Chemotherapy 36: 2085–2092, 1992

    Article  PubMed  CAS  Google Scholar 

  • Saxby MF, Arkell DG, Andrews JM, Wise R. Penetration of cefpirome into prostatic tissue. Journal of Antimicrobial Chemotherapy 25: 488–490, 1990

    Article  PubMed  CAS  Google Scholar 

  • Schäfer V, Shah PM, Doerr HW, Zieman M, Hellwich S, et al. In vitro activity of cefpirome against isolates from patients with urinary tract, lower respiratory tract and wound infections. Journal of Antimicrobial Chemotherapy 29 (Suppl. A): 7–12, 1992

    PubMed  Google Scholar 

  • Schentag JJ. Clinical significance of antibiotic tissue penetration. Clinical Pharmacokinetics 16 (Suppl. 1): 25–31, 1989

    Article  PubMed  CAS  Google Scholar 

  • Sugioka T, Asano T, Chikaraishi Y, Suzuki E, Sano A, et al. Stability and degradation pattern of cefpirome (HR-810) in aqueous solution. Chemical and Pharmaceutical Bulletin 38: 1998–2002, 1990

    Article  CAS  Google Scholar 

  • Tabata S, Shimura T, Maeda T, Hayashi S. Protein binding of cefpirome sulfate in man and animals and its displacing effect on bilirubin bound to human serum albumin. Chemotherapy (Tokyo) 39 (Suppl. 1): 109–114, 1991

    CAS  Google Scholar 

  • Täuber MG, Sande MA. General principles of therapy of pyogenic meningitis. Infectious Disease Clinics of North America 4: 661–676, 1990

    PubMed  Google Scholar 

  • Tullus K, Olsson-Liljequist B, Lundström G, Burman LG. Antibiotic susceptibility of 629 bacterial blood and CSF isolates from Swedish infants and therapeutic implications. Acta Paediatrica Scandinavica 80: 205–212, 1991

    Article  PubMed  CAS  Google Scholar 

  • Turley CP, Kearns GL, Jacobs RF. Microanalytical high-performance liquid chromatography assay for cefpirome (HR 810) in serum. Antimicrobial Agents and Chemotherapy 32: 1481–1483, 1988

    Article  PubMed  CAS  Google Scholar 

  • Uihlein M, Kiesel N, Seeger K. Determination of cefpirome (HR 810) in serum and urine. Infection 16: 135–140, 1988

    Article  PubMed  CAS  Google Scholar 

  • Valcke Y, Pauwels R, Van Der Straeten M. Pharmacokinetics of antibiotics in the lungs. European Respiratory Journal 3: 715–722, 1990

    PubMed  CAS  Google Scholar 

  • Verho M, Maass L, Malerczyk V, Grötsch H. Renal tolerance of cefpirome (HR 810), a new cephalosporin antibiotic. Infection 15: 215–219, 1987

    Article  PubMed  CAS  Google Scholar 

  • Vogelman B, Gudmundsson S, Leggett J, Turnidge J, Ebert S, et al. Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy in an animal model. Journal of Infectious Diseases 158: 831–847, 1988

    Article  PubMed  CAS  Google Scholar 

  • Wheat PF, Spencer RC. In vitro activity of cefpirome (HR 810) against Enterococcus species. European Journal of Microbiology and Infectious Diseases 9: 235–237, 1990

    Article  CAS  Google Scholar 

  • Wise R. Methods for evaluating the penetration of β-lactam antibiotics into tissues. Reviews of Infectious Diseases 8 (Suppl. 3): s325–s332, 1986

    Article  PubMed  CAS  Google Scholar 

  • Wise R, Andrews JM, Cross C, Piddock JV. The antimicrobial activity of cefpirome, a new cephalosporin. Journal of Antimicrobial Chemotherapy 15: 449–456, 1985

    Article  PubMed  CAS  Google Scholar 

  • Wolff M, Chavanet P, Kazmierczak A, Pechinot A, Dematons C, et al. Diffusion of cefpirome into the cerebrospinal fluid of patients with purulent meningitis. Journal of Antimicrobial Chemotherapy 29 (Suppl. A): 59–62, 1992

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, 3 Gates Circle, Buffalo, NY, 14209, USA

    Laura C. Strenkoski &  David E. Nix (Assistant Director)

  2. School of Pharmacy, State University of New York at Buffalo, Buffalo, New York, USA

    Laura C. Strenkoski &  David E. Nix (Assistant Director)

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  1. Laura C. Strenkoski
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  2. David E. Nix
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Strenkoski, L.C., Nix, D.E. Cefpirome Clinical Pharmacokinetics. Clin. Pharmacokinet. 25, 263–273 (1993). https://doi.org/10.2165/00003088-199325040-00002

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