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Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: Gentamicin in burn patients

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Abstract

A general approach to the establishment of dosing regimens for drug administration by multiple intravenous infusions is presented. The method is applicable where the elimination kinetics are first order and can be represented by a one-compartment open model. The approach utilizes serum concentration-time data obtained during any dosing interval for the calculation of the apparent distribution volume and the half-life in individual patients. These values are then used to individualize the dosing regimen where it is required to maintain serum concentrations of the drug within a desired range. Estimation of kinetic parameters for gentamicin in burn patients with normal or only slightly reduced renal function demonstrates a relatively constant distribution volume of 0.25 ± 0.086 liter/kg (mean ± sd)but a relatively variable half-life of 2.1 ± 1.3 hr. This finding supports the view that gentamicin regimens should be individualized even in patients with essentially normal renal function.

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References

  1. M. C. McHenry, T. L. Gavan, R. W. Gifford, Jr., N. A. Geurkink, R. A. Van Ommen, M. A. Town, and J. G. Wagner. Gentamicin dosages for renal insufficiency.Ann. Int. Med. 74:192–197 (1971).

    Article  CAS  PubMed  Google Scholar 

  2. D. Kaye, M. E. Levison, and E. D. Labovitz. The unpredictability of serum concentrations of gentamicin: Pharmacokinetics of gentamicin in patients with normal and abnormal renal function.J. Infect. Dis. 130:150–154 (1974).

    Article  CAS  PubMed  Google Scholar 

  3. A. M. Gyselynck, A. Forrey, and R. Cutler. Pharmacokinetics of gentamicin: Distribution and plasma and renal clearance.J. Infect. Dis. Suppl. 124:S70-S76 (1971).

    Article  CAS  PubMed  Google Scholar 

  4. E. L. Goodman, J. Van Gelder, R. K. Holmes, A. R. Hull, and J. P. Sanford. Gentamicin serum levels, dose response, and nephrotoxicity. Abstracts of the 14th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, 1974.

  5. J. C. Gingell and P. M. Waterworth. Dose of gentamicin in patients with normal renal function and renal impairment.Brit. Med. J. 2:19–22 (1968).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. R. E. Cutler, A. M. Gyselynck, W. P. Fleet, and A. W. Forrey. Correlation of serum creatinine concentration and gentamicin half-life.J. Am. Med. Assoc. 219:1037–1041 (1972).

    Article  CAS  Google Scholar 

  7. R. A. Chan, E. J. Benner, and P. D. Hoeprich. Gentamicin therapy in renal failure: A nomogram for dosage.Ann. Int. Med. 76:773–778 (1972).

    Article  CAS  PubMed  Google Scholar 

  8. G. E. Mawer, R. Ahmad, S. M. Dobbs, J. G. McGough, S. B. Lucus, and J. A. Tooth. Prescribing aids for gentamicin.Brit. J. Clin. Pharmacol. 1:45–50 (1974).

    Article  CAS  Google Scholar 

  9. M. E. Lund, D. J. Blazevic, and J. M. Matsen. Rapid gentamicin bioassay using a multiple-antibiotic-resistant strain ofKlebsiella pneumoniae.Antimicrob. Agents Chemother. 4: 569–573 (1973).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. H. O. Hartley. The modified Gauss-Newton method for the fitting of nonlinear regression functions by least squares.Technometrics 3:269–280 (1961).

    Article  Google Scholar 

  11. H. O. Hartley and A. Booker. Non-linear least squares estimation.Ann. Math. Stat. 36: 638–650 (1965).

    Article  Google Scholar 

  12. J. W. Paisley, A. L. Smith, and D. H. Smith. Gentamicin in newborn infants.Am. J. Dis. Child. 126:473–477 (1973).

    Article  CAS  PubMed  Google Scholar 

  13. G. H. McCracken, Jr.. Clinical pharmacology of gentamicin in infants 2 to 24 months of age.Am. J. Dis. Child. 124:884–887 (1972).

    PubMed  Google Scholar 

  14. J. B. Scarborough.Numerical Mathematical Analysis, 6th ed., Johns Hopkins Press, Baltimore, 1966, pp. 551–552.

    Google Scholar 

  15. M. Barza, R. B. Brown, D. Shen, M. Gibaldi, and L. Weinstein. Predictability of blood levels of gentamicin in man.J. Infect. Dis. 132:165–174 (1975).

    Article  CAS  PubMed  Google Scholar 

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NIH Grant RR-267 supported our use of the computer within the Health Computer Sciences Facility at the University of Minnesota.

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Sawchuk, R.J., Zaske, D.E. Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: Gentamicin in burn patients. Journal of Pharmacokinetics and Biopharmaceutics 4, 183–195 (1976). https://doi.org/10.1007/BF01086153

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