Skip to main content
SpringerLink
Log in

Individualising Gentamicin Dosage Regimens

A Comparative Review of Selected Models, Data Fitting Methods and Monitoring Strategies

  • Review Article
  • Clinical Pharmacokinetic Concepts
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

The various components required for individualising clinical drug dosage regimens are reviewed, including a study of 3 types of fitting procedures, 2 types of gentamicin pharmacokinetic model and the utility of D-optimal times for obtaining serum gentamicin concentrations.

The combination of the current Bayesian fitting procedure, the kslope pharmacokinetic model [in which the elimination rate constant (kel) can change from dose to dose with changing creatinine clearance] and the explicit measurement of the assay error pattern yielded predictions of future serum gentamicin concentrations which were (a) slightly better than those found using weighted nonlinear least squares; (b) somewhat better than those found with Bayesian fitting and a fixed-kel model; (c) better than those found using the traditional linear regression fitting procedure and a fixed kel model. D-Optimally timed pairs of concentrations also predicted future concentrations at least as well, and more cost effectively.

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

  • Box GEP, Lucas HL. Design of experiments in nonlinear situations. Biometrika 46: 77–90, 1959

    Google Scholar 

  • Brooker G, Jelliffe RW. Serum cardiac glycoside assay based upon displacement of 3H-ouabain from Na+-K+-ATPase. Circulation 45: 20–36, 1972

    Article  PubMed  CAS  Google Scholar 

  • Burton ME, Cho MSS, Platt DR, Day BR, Brater DC, et al. Accuracy of Bayesian and Sawchuk-Zaske dosing methods for gentamicin. Clinical Pharmacy 5: 143–149, 1986

    PubMed  CAS  Google Scholar 

  • Caceci MS, Cacheris WP. Fitting curves to data: the simplex algorithm is the answer. BYTE Magazine May: 340–362, 1984

    Google Scholar 

  • Chrystyn H. Validation of the use of Bayesian analysis in the optimization of gentamicin therapy from the commencement of dosing. Drug Intelligence and Clinical Pharmacy 22: 49–53, 1988

    PubMed  CAS  Google Scholar 

  • De Groot MH. Probability and statistics, pp. 359–360, Addison-Wesley Publishing Co., Reading, Mass., 1975

    Google Scholar 

  • Dettli L, Spring P, Habersang R. Drug dosage in patients with impaired renal function. Postgraduate Medicine 46: 32–35, 1970

    Article  Google Scholar 

  • Drusano G, Forrest A, Plaisance K, Wade J. A prospective evaluation of optimal sampling theory in the determination of the steady-state pharmacokinetics of piperacillin in febrile neutropenic cancer patients. Clinical Pharmacology and Therapeutics 45: 635–642, 1989

    Article  PubMed  CAS  Google Scholar 

  • Drusano G, Forrest A, Snyder M, Reed M, Blumer J. An evaluation of optimal sampling strategy and adaptive study design. Clinical Pharmacology and Therapeutics 44: 232–288, 1988

    Article  PubMed  CAS  Google Scholar 

  • D’Argenio DZ. Optimal sampling times for pharmacokinetic experiments. Journal of Pharmacokinetics and Biopharmaceutics 9: 739–756, 1981

    PubMed  Google Scholar 

  • Finney DJ. Probit analysis, pp. 8–20, Cambridge University Press, Cambridge, 1947

    Google Scholar 

  • Gilman TM, Mohler PA, Muir KT, Gill MA. Evaluation of Bayesian methods to predict measured gentamicin concentrations. Drug Intelligence and Clinical Pharmacy 20: 469, 1986

    Google Scholar 

  • Godley PJ, Black J, Frohna PA, Garrelts JC. Comparison of a new Bayesian program with three different microcomputer programs for predicting gentamicin concentrations. Drug Intelligence and Clinical Pharmacy 20: 468–469, 1986

    Google Scholar 

  • Huang M, Slugg P, Lochrem J, Brynes J. High dose aminoglycoside therapy in surgical ICU patients. Clinical Pharmacology and Therapeutics 47: 208, 1990

    Google Scholar 

  • Hurst AK, Iglesias T, Jelliffe RW, Gilman T, D’Argenio DZ. Population pharmacokinetics of gentamicin in internal medicine patients. Drug Intelligence and Clinical Pharmacy 111: 469, 1985

    Google Scholar 

  • Hurst AK, Iseri K, Gill M, Noguchi J, Gilman T, et al. Comparison of four methods for predicting serum gentamicin concentrations in surgical patients with perforated or gangrenous appendicitis. Clinical Pharmacy 6: 234–238, 1987

    PubMed  CAS  Google Scholar 

  • Iglesias T. Control adaptado de niveles sericos de gentamicina: analisis de tres métodos diferentes, Ph.D Thesis, School of Pharmacy, University of Salamanca, 1985

  • Jelliffe RW. A mathematical analysis of digitalis kinetics in patients with normal and reduced renal function. Mathematical Biosciences 1: 305–330, 1967

    Article  CAS  Google Scholar 

  • Jelliffe RW. An improved method of digoxin therapy. Annals of Internal Medicine 69: 703–717, 1968

    PubMed  CAS  Google Scholar 

  • Jelliffe RW, Buell J, Kalaba R, Sridhar R, Rockwell R, et al. An improved method of digitoxin therapy. Annals of Internal Medicine 72: 453–464, 1970

    PubMed  CAS  Google Scholar 

  • Jelliffe RW. Clinical applications of pharmacokinetics and control theory. In Maronde (Ed.) Topics in clinical pharmacology and therapeutics, pp. 57–80, Springer-Verlag, New York, 1986

    Google Scholar 

  • Jelliffe RW. Creatinine clearance: bedside estimate. Annals of Internal Medicine 79: 604–605, 1973

    PubMed  CAS  Google Scholar 

  • Jelliffe RW, D’Argenio DZ, Rodman J, Schumitzky A. A timeshared computer program for adaptive control of lidocaine therapy, using an optimal strategy for obtaining serum concentrations. Proceedings of the Fourth Annual Symposium on Computer Applications in Medical Care, Washington, November, 1980

  • Jelliffe RW, D’Argenio DZ, Schumitzky A, Hu L, Liu M. The USC PC-PACK programs for planning, monitoring, and adjusting drug dosage regimens. Proceedings of the 23rd Annual Meeting of the Association for the Advancement of Medical Instrumentation, Washington, May 14–18, p. 51, 1988a (available from the first author through a noncommerical licence agreement with the University of Southern California)

  • Jelliffe RW, Jelliffe SM. A computer program for estimation of creatinine clearance from unstable serum creatinine levels, age, sex, and weight. Mathematical Biosciences 14: 17–29, 1972

    Article  Google Scholar 

  • Jelliffe RW. Reductions of digitalis toxicity by computer-assisted glycoside dosage regimens. Annals of Internal Medicine 77: 891–906, 1972

    PubMed  CAS  Google Scholar 

  • Jelliffe RW, Schumitzky A, D’Argenio DZ, Katz D, Nicholson WF, et al. Time-shared computer programs for M.A.P. Bayesian forecasting and adaptive control of dosage regimens of lidocaine, aminoglycosides, procainamide, digoxin, digitoxin, and quinidine, with optimal monitoring strategies and automatic delivery of infusion protocols. Proceedings of the 2nd World Congress on Clinical Pharmacology and Therapeutics, Washington, July 31–August 5, p. 46, 1983

  • Jelliffe RW, Schumitzy A, D’Argenio D, Katz D, Nicholson W, et al. Timeshared computer programs for M.A.P. Bayesian adaptive control of dosage regimens of aminoglycosides, lidocaine, digoxin, digitoxin, procainamide, and quinidine. In Bonal & Poston (Eds) Progress in clinical pharmacy VI: Proceedings of the 12th European Symposium on Clinical Pharmacy, Barcelona, October 1983, pp. 173–176, Cambridge University Press, Cambridge, 1983

    Google Scholar 

  • Jelliffe RW. Time-shared computer programs for therapeutic drug monitoring and adaptive control of dosage regimens. In Moyer & Boeckx (Eds) Applied therapeutic drug monitoring, Vol 1, pp. 133–153, American Association for Clinical Chemistry, Washington, 1982

    Google Scholar 

  • Jelliffe R. Explicit determination of laboratory assay errors — a useful aid in therapeutic drug monitoring. In ASCP Drug monitoring and toxicology check sample, Vol. 10, No. DM 89-4 (DM-56), pp. 1–5, American Society of Clinical Pathologists, Chicago, 1989

    Google Scholar 

  • Jelliffe R, Iglesias T, Rodriguez J, Hurst A, Foo K. Factors affecting precise control of serum drug levels in patients. In Cobelli & Mariani (Eds) Preprints of the IFAC Symposium on Modelling and Control in Biomedical Systems, Venice, April 6–8, 1988, pp. 86–88, Pergamon Press, 1988b

  • Landaw E. Optimal design for individual parameter estimation in pharmacokinetics. In Rowland et al. (Eds) Variation in drug therapy: description, estimation and control, pp. 187–200, Raven Press, New York, 1985

    Google Scholar 

  • Maire P, Jelliffe R, Dumarest C, Roux D, Breant V, et al. Controle adaptatif optimal des posologies: expérience des aminosides en gériatrie. In Venot & Degoulet (Eds) Informatique et medicaments. Comptes Rendus du Colloque AIM-IF et IRT, Paris, December 1989, Informatique et Santé, Vol. 2, pp. 154–169, Springer Verlag, Paris, 1989

    Google Scholar 

  • Neider JA, Mead R. A simplex method for function minimization. Computer Journal 7: 308–313, 1965

    Google Scholar 

  • Rodman JH, Jelliffe RW, Kolb E, Tuey DB, de Guzman, et al. Clinical studies with computer-assisted initial lidocaine therapy. Archives of Internal Medicine 144: 703–709, 1984

    Article  PubMed  CAS  Google Scholar 

  • Sawchuk R, Zaske D. Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: gentamicin in burn patients. Journal of Pharmacokinetics and Biopharmaceutics 4: 183–195, 1976

    PubMed  CAS  Google Scholar 

  • Sheiner LB, Beal S, Rosenberg B, Marathe V, et al. Forecasting individual pharmacokinetics. Clinical Pharmacology and Therapeutics 31: 294–305, 1979

    Google Scholar 

  • Vožeh S, Kaufman G, Uematsu T, Follath F. Computer-assisted lidocaine dosage using adaptive feedback method. In Cobell & Mariani (Eds) Preprints of the IFAC Symposium on Modelling and Control in Biomedical Systems, Venice, April 6–8, 1988, pp. 595–599, Pergamon Press, 1988

  • Vožeh S, Steimer JL. Feedback control methods for drug dosage optimization. Clinical Pharmacokinetics 10: 457–476, 1985

    Article  PubMed  Google Scholar 

  • Zaske D, Cipolle R. Aminoglycoside dosing program, 2nd ed., 1983

Download references

Author information

Authors and Affiliations

  1. Laboratory of Applied Pharmacokinetics, University of Southern California, Schools of Medicine and Pharmacy, Los Angeles, California, USA

    Roger W. Jelliffe, Teresa Iglesias, Agneta K. Hurst, Kimberley A. Foo & Julian Rodriguez

Authors
  1. Roger W. Jelliffe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Teresa Iglesias
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Agneta K. Hurst
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kimberley A. Foo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Julian Rodriguez
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jelliffe, R.W., Iglesias, T., Hurst, A.K. et al. Individualising Gentamicin Dosage Regimens. Clin. Pharmacokinet. 21, 461–478 (1991). https://doi.org/10.2165/00003088-199121060-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-199121060-00006

Keywords

Search

Navigation