This Article Full Text (PDF) Other Versions of this Article: AAC.00194-08v1 52/9/3035    most recent 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 Google Scholar Articles by DiCenzo, R. Articles by Schifitto, G. PubMed PubMed Citation Articles by DiCenzo, R. Articles by Schifitto, G.

 Previous Article  |  Next Article 

Antimicrob. Agents Chemother. doi:10.1128/AAC.00194-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Effects of Minocycline and Valproic acid Coadministration on Atazanavir Plasma Concentrations in HIV-infected Adults Receiving Atazanavir/Ritonavir

University at Buffalo, Buffalo, New York; University of Rochester, Rochester, New York; University of North Carolina, Chapel Hill, NC

^* To whom correspondence should be addressed. Email: robert_dicenzo{at}urmc.rochester.edu.

	Abstract

Background: Minocycline and valproic acid are potential adjuvant therapies for the treatment of HIV-associated cognitive impairment. The purpose of the study was to determine if minocycline alone or in combination with valproic acid affected atazanavir plasma concentrations.

Methods: Twelve adult HIV-infected subjects whose regimen included atazanavir/ritonavir 300/100 mg daily for at least 4 weeks were enrolled. Each subject received atazanavir/ritonavir on Day 1, atazanavir/ritonavir plus minocycline 100 mg twice daily on Days 2 - 15, and atazanavir/ritonavir plus minocycline 100 mg twice daily and valproic acid 250 mg twice daily on Days 16 – 30 with meals. Subjects had 11 plasma samples drawn over a dosing interval on Days 1, 15, and 30.

Results: Minocycline and valproic acid coadministration was well tolerated in all 12 subjects (6 male; mean (SD) age = 43.1 (8.2) years). The geometric mean ratio (GMR (95% CI)) for atazanvir AUC_24h, Cmin and Cmax with and without minocycline was 0.67 (0.50 – 0.90), 0.50 (0.28 – 0.89) and 0.75 (0.58 – 0.95), respectively. Similar decreases in atazanavir exposure were seen after the addition of valproic acid. The GMR (95% CI) for atazanavir AUC_24h, Cmin and Cmax with and without minocycline plus valproic acid was 0.68 (0.43 – 1.06), 0.50 (0.24 – 1.06) and 0.66 (0.41 – 1.06), respectively. Neither minocycline nor minocycline plus valproic acid coadministration appeared to influence the plasma concentrations of ritonavir (p > 0.2).

Conclusions: Minocycline coadministration resulted in decreased atazanavir exposure and there was no evidence that the addition of valproic acid mediated this effect.