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Antimicrobial Agents and Chemotherapy, September 2008, p. 3035-3039, Vol. 52, No. 9
0066-4804/08/$08.00+0 doi:10.1128/AAC.00194-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Effects of Minocycline and Valproic Acid Coadministration on Atazanavir Plasma Concentrations in Human Immunodeficiency Virus-Infected Adults Receiving Atazanavir-Ritonavir
Robert DiCenzo,1,2*
Derick R. Peterson,2
Kim Cruttenden,2
Peter Mariuz,2
Naser L. Rezk,3
Jill Hochreiter,1
Harris Gelbard,2 and
Giovanni Schifitto2
University at Buffalo, Buffalo, New York,1 University of Rochester, Rochester, New York,2 University of North Carolina, Chapel Hill, North Carolina3
Received 11 February 2008/ Returned for modification 4 April 2008/ Accepted 11 June 2008
Minocycline and valproic acid are potential adjuvant therapies for the treatment of human immunodeficiency virus (HIV)-associated cognitive impairment. The purpose of this study was to determine whether minocycline alone or in combination with valproic acid affected atazanavir plasma concentrations. Twelve adult HIV-infected subjects whose regimen included atazanavir (300 mg)-ritonavir (100 mg) daily for at least 4 weeks were enrolled. Each subject received atazanavir-ritonavir on day 1, atazanavir-ritonavir plus 100 mg minocycline twice daily on days 2 to 15, and atazanavir-ritonavir plus 100 mg minocycline twice daily and 250 mg valproic acid twice daily on days 16 to 30 with meals. The subjects had 11 plasma samples drawn over a dosing interval on days 1, 15, and 30. The coadministration of minocycline and valproic acid with atazanavir-ritonavir was well tolerated in all 12 subjects (six male; mean [± standard deviation] age was 43.1 [8.2] years). The geometric mean ratios (GMRs; 95% confidence interval [CI]) for the atazanavir area under the concentration-time curve from 0 to 24 h at steady state (AUC0-24), the plasma concentration 24 h after the dose (Cmin), and the maximum concentration during the dosing interval (Cmax) with and without minocycline were 0.67 (0.50 to 0.90), 0.50 (0.28 to 0.89), and 0.75 (0.58 to 0.95), respectively. Similar decreases in atazanavir exposure were seen after the addition of valproic acid. The GMRs (95% CI) for atazanavir AUC0-24, Cmin, and Cmax with and without minocycline plus valproic acid were 0.68 (0.43 to 1.06), 0.50 (0.24 to 1.06), and 0.66 (0.41 to 1.06), respectively. Coadministration of neither minocycline nor minocycline plus valproic acid appeared to influence the plasma concentrations of ritonavir (P > 0.2). Minocycline coadministration resulted in decreased atazanavir exposure, and there was no evidence that the addition of valproic acid mediated this effect.
* Corresponding author. Mailing address: University of Rochester Medical Center, Infectious Disease Division, 601 Elmwood Avenue, Box 689, Room 3-6209, Rochester, NY 14642. Phone: (585) 275-6249. Fax: (585) 442-9328. E-mail: robert_dicenzo{at}urmc.rochester.edu
Published ahead of print on 23 June 2008.
Antimicrobial Agents and Chemotherapy, September 2008, p. 3035-3039, Vol. 52, No. 9
0066-4804/08/$08.00+0 doi:10.1128/AAC.00194-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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