Abstract
The objective of this study was to determine whether differences in tissue accumulation observed upon multiple dosing of aminoglycosides in hospitalized patients could be identified in appropriate single-dose studies in normal volunteers. Ten volunteers received single intravenous doses of 1.0 mg of gentamicin and tobramycin per kg of body weight in randomized crossover fashion. Multiple serum and urine samples were collected during the next 30 days. Serum aminoglycoside concentrations and urinary excretion rates were fitted to a two-compartment pharmacokinetic model, and parameters were derived. Tobramycin exhibited a higher clearance (P less than 0.08) and a lower volume of distribution at steady state (P less than 0.1), neither of which was significant. Tobramycin also showed a significantly lower predicted amount of drug in the body at steady state (P less than 0.05). These differences are consistent with observations made in patients receiving multiple doses. Single-dose studies appear to be capable of discriminating pharmacokinetic characteristics relevant to the comparative nephrotoxic potential of these two aminoglycosides.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Cronin R. E., Bulger R. E., Southern P., Henrich W. L. Natural history of aminoglycoside nephrotoxicity in the dog. J Lab Clin Med. 1980 Mar;95(3):463–474. [PubMed] [Google Scholar]
- Hewitt W. L. Gentamicin: toxicity in perspective. Postgrad Med J. 1974 Nov;50 (Suppl 7):55–61. [PubMed] [Google Scholar]
- Hottendorf G. H., Gordon L. L. Comparative low-dose nephrotoxicities of gentamicin, tobramycin, and amikacin. Antimicrob Agents Chemother. 1980 Jul;18(1):176–181. doi: 10.1128/aac.18.1.176. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kahlmeter G., Jonsson S., Kamme C. Multiple-compartment pharmacokinetics of tobramycin. J Antimicrob Chemother. 1978 May;4 (Suppl A):5–11. doi: 10.1093/jac/4.suppl_a.5. [DOI] [PubMed] [Google Scholar]
- Panwalker A. P., Malow J. B., Zimelis V. M., Jackson G. G. Netilmicin: clinical efficacy, tolerance, and toxicity. Antimicrob Agents Chemother. 1978 Feb;13(2):170–176. doi: 10.1128/aac.13.2.170. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schentag J. J., Cumbo T. J., Jusko W. J., Plaut M. E. Gentamicin tissue accumulation and nephrotoxic reactions. JAMA. 1978 Nov 3;240(19):2067–2069. [PubMed] [Google Scholar]
- Schentag J. J., Gengo F. M., Plaut M. E., Danner D., Mangione A., Jusko W. J. Urinary casts as an indicator of renal tubular damage in patients receiving aminoglycosides. Antimicrob Agents Chemother. 1979 Oct;16(4):468–474. doi: 10.1128/aac.16.4.468. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schentag J. J., Jusko W. J. Renal clearance and tissue accumulation of gentamicin. Clin Pharmacol Ther. 1977 Sep;22(3):364–370. doi: 10.1002/cpt1977223364. [DOI] [PubMed] [Google Scholar]
- Schentag J. J., Lasezkay G., Cumbo T. J., Plaut M. E., Jusko W. J. Accumulation pharmacokinetics of tobramycin. Antimicrob Agents Chemother. 1978 Apr;13(4):649–656. doi: 10.1128/aac.13.4.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schentag J. J., Lasezkay G., Plaut M. E., Jusko W. J., Cumbo T. J. Comparative tissue accumulation of gentamicin and tobramycin in patients. J Antimicrob Chemother. 1978 May;4 (Suppl A):23–30. doi: 10.1093/jac/4.suppl_a.23. [DOI] [PubMed] [Google Scholar]
- Schentag J. J., Plaut M. E., Cerra F. B. Comparative nephrotoxicity of gentamicin and tobramycin: pharmacokinetic and clinical studies in 201 patients. Antimicrob Agents Chemother. 1981 May;19(5):859–866. doi: 10.1128/aac.19.5.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scherberich J. E., Falkenberg F. W., Mondorf A. W., Müller H., Pfleiderer G. Biochemical and immunological studies on isolated brush border membranes of human kidney cortex and their membrane surface proteins. Clin Chim Acta. 1974 Sep 16;55(2):179–197. doi: 10.1016/0009-8981(74)90294-0. [DOI] [PubMed] [Google Scholar]
- Smith C. R., Lipsky J. J., Laskin O. L., Hellmann D. B., Mellits E. D., Longstreth J., Lietman P. S. Double-blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin. N Engl J Med. 1980 May 15;302(20):1106–1109. doi: 10.1056/NEJM198005153022002. [DOI] [PubMed] [Google Scholar]
