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Antimicrobial Agents and Chemotherapy, October 2006, p. 3336-3342, Vol. 50, No. 10
0066-4804/06/$08.00+0     doi:10.1128/AAC.00461-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Effect of Rifampin on Steady-State Pharmacokinetics of Atazanavir with Ritonavir in Healthy Volunteers{dagger}

D. M. Burger,1,2* S. Agarwala,3 M. Child,3 A. Been-Tiktak,4 Y. Wang,3 and R. Bertz3

Radboud University Medical Center,1 Nijmegen University Center for Infectious Diseases, Nijmegen, The Netherlands,2 Bristol-Myers Squibb, Princeton, New Jersey,3 Bristol-Myers Squibb, Woerden, The Netherlands4

Received 13 April 2006/ Returned for modification 19 May 2006/ Accepted 6 July 2006

Mycobacterium tuberculosis is a concern in patients with human immunodeficiency virus (HIV) infection. Rifampin (RIF), an agent used against M. tuberculosis, is contraindicated with most HIV protease inhibitors. Atazanavir (ATV) has clinical efficacy comparable to a standard of care regimen in naive patients and, when dosed with low-dose ritonavir (RTV), also in treatment-experienced patients. We evaluated here the safety and pharmacokinetics of ATV, resulting from three regimens of ATV, RTV, and RIF in 71 healthy subjects. The pharmacokinetics for ATV and RTV were assessed after 6 and 10 days of dosing with ATV 400 mg (n = 53) and with ATV-RTV at 300 and 100 mg (ATV/RTV 300/100; n = 52), respectively. Steady-state pharmacokinetics for ATV, RTV, RIF, and desacetyl-rifampin (des-RIF) were measured after 10 days of dosing of ATV/RTV/RIF 300/100/600 (n = 17), ATV/RTV/RIF 300/200/600 (n = 17), or ATV/RTV/RIF 400/200/600 (n = 14). An RIF 600-alone arm was enrolled as a control group (n = 18). With ATV/RTV/RIF 400/200/600, ATV area under the concentration-time curve values were comparable, but the Cmin values were lower relative to ATV 400 alone. ATV exposures were substantially reduced for the other RIF-containing regimens relative to ATV 400 alone and for all regimens relative to ATV/RTV 300/100 alone. RIF and des-RIF exposures were 1.6- to 2.5-fold higher than with RIF 600 alone. The incidence of grade 3/4 alanine aminotransferase/aspartate aminotransferase values was limited to 1 subject each in both the ATV/RTV/RIF 300/200/600 and the ATV/RTV/RIF 400/200/600 treatments. Coadministration of ATV with RIF was safe and generally well tolerated. Since ATV exposures were reduced in all regimens, ATV and RIF should not be coadministered at the dosing regimens studied.

* Corresponding author. Mailing address: Department of Clinical Pharmacy, 864 Radboud UMC Nijmegen, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands. Phone: 31 24 3616406. Fax: 31 24 3668755. E-mail: D.Burger{at}akf.umcn.nl.

{dagger} Supplemental material for this article may be found at http://aac.asm.org/.

Antimicrobial Agents and Chemotherapy, October 2006, p. 3336-3342, Vol. 50, No. 10
0066-4804/06/$08.00+0     doi:10.1128/AAC.00461-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Luber, A. D. (2008). Pharmacokinetic Considerations for Selection of HAART in Treatment-Naive HIV-Infected Individuals, 2008: More Than It Seems?. J Int Assoc Physicians AIDS Care (Chic Ill) 7: 10-16 [Abstract]  
  • Ribera, E., Azuaje, C., Lopez, R. M., Domingo, P., Curran, A., Feijoo, M., Pou, L., Sanchez, P., Sambeat, M. A., Colomer, J., Lopez-Colomes, J. L., Crespo, M., Falco, V., Ocana, I., Pahissa, A. (2007). Pharmacokinetic interaction between rifampicin and the once-daily combination of saquinavir and low-dose ritonavir in HIV-infected patients with tuberculosis. J Antimicrob Chemother 59: 690-697 [Abstract] [Full Text]  


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