This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Horton, C. M. Articles by Anderson, R. Search for Related Content PubMed PubMed Citation Articles by Horton, C. M. Articles by Anderson, R.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, Oct 1995, 2309-2315, Vol 39, No. 10
Copyright © 1995 by the American Society for Microbiology. All rights reserved.

Population pharmacokinetics of stavudine (d4T) in patients with AIDS or advanced AIDS-related complex

CM Horton, MN Dudley, S Kaul, KH Mayer, K Squires, L Dunkle and R Anderson
Antiinfective Pharmacology Research Unit, University of Rhode Island College of Pharmacy, Roger Williams Medical Center, Providence 02908, USA.

The population pharmacokinetics and bioavailability of oral stavudine (d4T; 2',3'-dideoxy-3'-deoxythymidine) was determined in 81 patients with AIDS or AIDS-related complex (ARC) enrolled in phase I and phase I/II dose-ranging trials. Each patient underwent inpatient pharmacokinetic studies following administration of the first oral stavudine dose; 59 patients were restudied after chronic therapy for an average of 19 days. Thirty-three of these patients also received a single intravenous stavudine dose prior to starting an oral regimen. A two-compartment model with first-order absorption and elimination was used as the structural pharmacokinetic model. A basic model provided the following population parameter estimates (interpatient variability expressed in parentheses as percent coefficient of variation): clearance/bioavailability = 30.9 (24.5%) liters/h; volume of distribution/bioavailability = 8.42 (not modeled) liters; volume of distribution at steady state/bioavailability = 68.9 (105%) liters; intercompartmental clearance/bioavailability = 12.4 (26%) liters/h; and first-order absorption rate constant = 1.32 (78.9%) liters/h. In the subset of 33 patients receiving both intravenous and oral doses, the bioavailability of stavudine was estimated to be 99.1% (18.5%). Total body weight, stage of disease (AIDS versus ARC), and an oral stavudine dose of > or = 200 mg were found to have a statistically significant but a clinically marginal effect on the estimate of the oral clearance of stavudine. This analysis shows the high degree of bioavailability of stavudine in patients with AIDS and ARC and the relatively low degree of interpatient variability in oral drug clearance compared with those of other nucleosides. Population pharmacokinetic analysis is a useful tool for assessing the combined effects of several patient variables on the pharmacokinetic properties of drugs in human immunodeficiency virus- infected patients.

This article has been cited by other articles:

• Kwara, A., Lartey, M., Boamah, I., Rezk, N. L., Oliver-Commey, J., Kenu, E., Kashuba, A. D. M., Court, M. H. (2009). Interindividual Variability in Pharmacokinetics of Generic Nucleoside Reverse Transcriptase Inhibitors in TB/HIV-Coinfected Ghanaian Patients: UGT2B7*1c Is Associated With Faster Zidovudine Clearance and Glucuronidation. J Clin Pharmacol 49: 1079-1090 [Abstract] [Full Text]  
• ter Hofstede, H. J. M., Koopmans, P. P., Burger, D. M. (2008). Stavudine plasma concentrations and lipoatrophy. J Antimicrob Chemother 61: 933-938 [Abstract] [Full Text]  
• Narang, V. S., Lulla, A., Malhotra, G., Purandare, S. (2005). A Combined-Formulation Tablet of Lamivudine/Nevirapine/Stavudine: Bioequivalence Compared With Concurrent Administration of Lamivudine, Nevirapine, and Stavudine in Healthy Indian Subjects. J Clin Pharmacol 45: 265-274 [Abstract] [Full Text]  
• Chen, C.-L., Venkatachalam, T. K., Zhu, Z.-H., Uckun, F. M. (2001). In Vivo Pharmacokinetics and Metabolism of Anti-Human Immunodeficiency Virus Agent d4T-5'-[p-Bromophenyl Methoxyalaninyl Phosphate] (SAMPIDINE) in Mice. Drug Metab. Dispos. 29: 1035-1041 [Abstract] [Full Text]  
• Kaul, S., Kline, M. W., Church, J. A., Dunkle, L. M. (2001). Determination of Dosing Guidelines for Stavudine (2',3'-Didehydro-3'-Deoxythymidine) in Children with Human Immunodeficiency Virus Infection. Antimicrob. Agents Chemother. 45: 758-763 [Abstract] [Full Text]  
• Grasela, D. M., Stoltz, R. R., Barry, M., Bone, M., Mangold, B., O'Grady, P., Raymond, R., Haworth, S. J. (2000). Pharmacokinetics of Single-Dose Oral Stavudine in Subjects with Renal Impairment and in Subjects Requiring Hemodialysis. Antimicrob. Agents Chemother. 44: 2149-2153 [Abstract] [Full Text]  
• Kaul, S., Christofalo, B., Raymond, R. H., Stewart, M. B., Macleod, C. M. (1998). Effect of Food on the Bioavailability of Stavudine in Subjects with Human Immunodeficiency Virus Infection. Antimicrob. Agents Chemother. 42: 2295-2298 [Abstract] [Full Text]