PMID- 15673751 OWN - NLM STAT- MEDLINE DCOM- 20050329 LR - 20181113 IS - 0066-4804 (Print) IS - 1098-6596 (Electronic) IS - 0066-4804 (Linking) VI - 49 IP - 2 DP - 2005 Feb TI - Pharmacokinetic study of tenofovir disoproxil fumarate combined with rifampin in healthy volunteers. PG - 680-4 AB - Tenofovir disoproxil fumarate (tenofovir DF) was studied in combination with rifampin in 24 healthy subjects in a multiple-dose, open-label, single-group, two-period study. All subjects were given tenofovir DF at 300 mg once a day (QD) from days 1 to 10 (period 1). From days 11 to 20 the subjects received tenofovir DF at 300 mg combined with rifampin at 600 mg QD (period 2). The multiple-dose pharmacokinetics of tenofovir (day 10 and 20) and rifampin (day 20) were assessed. The drug-related adverse events (AEs) experienced during this study were mostly mild. Only one grade 3 AE possibly or probably related to the treatment (raised liver enzyme levels) occurred during period 2; the subject was withdrawn from the study. Pharmacokinetic data for 23 subjects were thus evaluable. Point estimates for the mean ratios of tenofovir with rifampin versus tenofovir alone for the area under the concentration-time curve from time zero to 24 h (AUC(0-24)), the maximum concentration of drug in plasma (C(max)), and the minimum concentration of drug in plasma (C(min)) were 0.88, 0.84, and 0.85, respectively. The 90% classical confidence intervals for AUC(0-24), C(max), and C(min) were 0.84 to 0.92, 0.78 to 0.90, and 0.80 to 0.91, respectively, thus suggesting pharmacokinetic equivalence. Similarly, coadministration of rifampin and tenofovir DF did not result in changes in the values of the tenofovir pharmacokinetic parameters. For rifampin, the values of the pharmacokinetic parameters found in this study were comparable to those found in the literature, indicating that tenofovir DF has no effect on the pharmacokinetics of rifampin. In conclusion, adaptation of either the rifampin or the tenofovir DF dose for the simultaneous treatment of tuberculosis and human immunodeficiency virus (HIV) infection in HIV-infected patients is probably not required. FAU - Droste, J A H AU - Droste JA AD - Department of Clinical Pharmacy, University Medical Centre Nijmegen, P.O. Box 9101, 533 KF, 6500 HB Nijmegen, The Netherlands. J.Droste@akf.umcn.nl FAU - Verweij-van Wissen, C P W G M AU - Verweij-van Wissen CP FAU - Kearney, B P AU - Kearney BP FAU - Buffels, R AU - Buffels R FAU - Vanhorssen, P J AU - Vanhorssen PJ FAU - Hekster, Y A AU - Hekster YA FAU - Burger, D M AU - Burger DM LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Antimicrob Agents Chemother JT - Antimicrobial agents and chemotherapy JID - 0315061 RN - 0 (Antibiotics, Antitubercular) RN - 0 (Antiviral Agents) RN - 0 (Drug Combinations) RN - 0 (Organophosphonates) RN - 99YXE507IL (Tenofovir) RN - JAC85A2161 (Adenine) RN - VJT6J7R4TR (Rifampin) SB - IM MH - Adenine/administration & dosage/adverse effects/*analogs & derivatives/*pharmacokinetics MH - Adult MH - Antibiotics, Antitubercular/administration & dosage/adverse effects/*pharmacokinetics MH - Antiviral Agents/administration & dosage/adverse effects/*pharmacokinetics MH - Chromatography, High Pressure Liquid MH - Drug Combinations MH - Drug Interactions MH - Female MH - Humans MH - Male MH - Middle Aged MH - Organophosphonates/administration & dosage/adverse effects/*pharmacokinetics MH - Rifampin/administration & dosage/adverse effects/*pharmacokinetics MH - Spectrometry, Fluorescence MH - Tenofovir PMC - PMC547290 EDAT- 2005/01/28 09:00 MHDA- 2005/03/30 09:00 PMCR- 2005/02/01 CRDT- 2005/01/28 09:00 PHST- 2005/01/28 09:00 [pubmed] PHST- 2005/03/30 09:00 [medline] PHST- 2005/01/28 09:00 [entrez] PHST- 2005/02/01 00:00 [pmc-release] AID - 49/2/680 [pii] AID - 0774-04 [pii] AID - 10.1128/AAC.49.2.680-684.2005 [doi] PST - ppublish SO - Antimicrob Agents Chemother. 2005 Feb;49(2):680-4. doi: 10.1128/AAC.49.2.680-684.2005.