Document Detail


Effect of rifampin on steady-state pharmacokinetics of atazanavir with ritonavir in healthy volunteers.
MedLine Citation:
PMID:  17005814     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 C(min) 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.
Authors:
D M Burger; S Agarwala; M Child; A Been-Tiktak; Y Wang; R Bertz
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  50     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-28     Completed Date:  2006-12-04     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3336-42     Citation Subset:  IM    
Affiliation:
Department of Clinical Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands. D.Burger@akf.umcn.nl
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MeSH Terms
Descriptor/Qualifier:
Anti-HIV Agents / administration & dosage,  adverse effects,  pharmacokinetics*
Area Under Curve
Drug Interactions
Drug Therapy, Combination
Enzyme Inhibitors / administration & dosage,  adverse effects,  pharmacokinetics*
Female
Humans
Male
Oligopeptides / administration & dosage,  adverse effects,  pharmacokinetics*
Pyridines / administration & dosage,  adverse effects,  pharmacokinetics*
Rifampin / administration & dosage,  adverse effects,  pharmacokinetics*
Ritonavir / administration & dosage,  adverse effects,  pharmacokinetics*
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Enzyme Inhibitors; 0/Oligopeptides; 0/Pyridines; 0/Ritonavir; 13292-46-1/Rifampin; 198904-31-3/atazanavir
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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