Pharmacokinetic interaction between rifampicin and ritonavir-boosted atazanavir in HIV-infected patients

Authors: Mallolas, J¹; Sarasa, M²; Nomdedeu, M¹; Soriano, A¹; López-Púa, Y²; Blanco, JL¹; Martínez, E¹; Gatell, JM¹

Source: HIV Medicine, Volume 8, Number 2, March 2007 , pp. 131-134(4)

Publisher: Wiley-Blackwell

Abstract:

Background

Tuberculosis (TB) is a common opportunistic infection among HIV-infected people, and rifampicin is an important drug for the treatment of TB. However, administration of rifampicin in combination with antiretroviral therapy, particularly protease inhibitors, is difficult because of drug-drug interactions. Methods

We have performed a prospective study in three HIV-infected patients with TB treated with a rifampicin-containing regimen (rifampicin 600 mg per day) and antiretroviral therapy including only nucleoside reverse transcriptase inhibitors (NRTIs) plus atazanavir 300 mg once a day (qd) and ritonavir 100 mg qd, to evaluate whether the inducing effect of rifampicin on the drug-metabolizing enzyme cytochrome P450 (CYP) 3A4 could be overcome by the inhibitory effect of ritonavir. A complete pharmacokinetic evaluation of the steady-state concentrations of atazanavir and ritonavir was performed. Results

In all three cases, more than 50% of the time the atazanavir level was below the minimum recommended trough plasma level (150 ng/mL according to current pharmacokinetic guidelines) to inhibit HIV wild-type replication. Conclusion

These results strongly indicate that the administration of rifampicin with a combination of atazanavir 300 mg qd plus ritonavir 100 mg qd must be avoided because subtherapeutic concentrations of atazanavir are produced.

Keywords: atazanavir; pharmacokinetic interaction; rifampicin

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1468-1293.2007.00442.x

Affiliations: 1: Infectious Diseases and 2: Pharmacology Service, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain

Publication date: 2007-03-01

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• In this Subject: Allergy & Immunology ,  Internal Medicine ,  Pediatrics
• By this author: Mallolas, J ;  Sarasa, M ;  Nomdedeu, M ;  Soriano, A ;  López-Púa, Y ;  Blanco, JL ;  Martínez, E ;  Gatell, JM

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