Abstract
A computer method has been investigated to differentiate the prenephrotoxic patient from the nontoxic patient by routine monitoring of serum gentamicin concentrations duringtherapy, without the need to discontinue medication. The method deliberately assumes an incorreect pharmacokinetic model and uses a nonlinear regression program to analyze data collected during continuous dosing. In principle, it appears that the prenephrotoxic patients may be identified on the basis of a decreasing “apparent” elimination rate constant of gentamicin during continuous therapy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
W. L. Hewitt. Gentamicin: Toxicity in perspective.Postgrad. Med. J. 50:55–59 (Suppl. 7) (1974).
J. J. Schentag and W. J. Jusko. Renal clearance and tissue accumulation of gentamicin in man.Clin. Pharmacol. Ther. 22:364–370 (1977).
M. Gibaldi and H. Weintraub. Some considerations as to the determination and significance of biological half-life.J. Pharm. Sci. 60:624–626 (1971).
J. J. Schentag, W. J. Jusko, J. W. Vance, T. J. Cumbo, E. Abrutyn, M. Delattre, and L. Gerbracht. Gentamicin disposition and tissue accumulation in multiple dosing.J. Pharmacokin. Biopharm. 5:559–577 (1977).
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).
R. A. Chan, E. J. Benner, and P. D. Hoeprich. Gentamicin therapy in renal failure: A nomogram for dosage.Ann. Intern. Med. 76:773–778 (1972).
M. C. McHenry, T. L. Gavan, R. W. Gifford, Jr., N. A. Geurkink, M. A. Town, and J. G. Wagner. Gentamicin dosages for renal insufficiency: Adjustments based on endogenous creatinine clearance and serum creatinine concentration.Ann. Intern. Med. 74:192–197 (1971).
W. A. Colburn, D. Shen, and M. Gibaldi. Pharmacokinetic analysis of drug concentration data obtained during repetitive drug administration. I.J. Pharmacokin. Biopharm. 4:469–485 (1976).
W. A. Colburn and M. Gibaldi. Pharmacokinetic analysis of drug concentration data obtained during repetitive drug administration. II.J. Pharm. Sci. 66:530–533 (1977).
Author information
Authors and Affiliations
Additional information
This work was supported in part by Grant No. GM-20852 from the National Institutes of Health.
Rights and permissions
About this article
Cite this article
Colburn, W.A., Schentag, J.J., Jusko, W.J. et al. A model for the prospective identification of the prenephrotoxic state during gentamicin therapy. Journal of Pharmacokinetics and Biopharmaceutics 6, 179–186 (1978). https://doi.org/10.1007/BF01312260
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF01312260