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Multiple-Dose Pharmacokinetics of Efavirenz with and without the Use of Rifampicin in HIV-Positive Patients

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Rifampicin (RIF) decreases serum concentrations of several antiretroviral drugs. We carried out a prospective, comparative study to define efavirenz (EFV) pharmacokinetics in 16 cases and 13 controls. Cases were HIV and tuberculosis (TB) co-infected adults assuming RIF 600 mg once daily and EFV 800 mg once daily. Patients on EFV at standard 600 mg dose without RIF were taken as controls. EFV levels in plasma were assayed by high-performance liquid chromatography (HLPC) predose (Ctrough) and at 1, 2, 3, 4, 5, 6, 8, 10, 11, 12, 13, 14, 16, 18, 22 and 24 hours post-dose, and pharmacokinetic parameters were determined by non-compartmental methods. Among cases, 81% were males, mean age was 37 years, 50% were Caucasians, mean weight was 64 kg, mean CD4 cell counts and log HIV RNA copies were 160/μl and 5.2 /μl, respectively. Cases had a significantly higher Cl/F/kg if compared with controls (0.269 ± 0.12 versus 0.167 + 0.05 L/h/kg, p<0.01). Otherwise, dose-dependent pharmacokinetic parameters of EFV were similar between cases and controls. Interindividual variability was consistently higher among TB cases compared to controls for all considered parameters. All cases completed combined treatment and no increased EFV toxicity was observed. These results suggest that a dose of 800 mg of EFV in association with rifampicin may be appropriate for patients of weight > 60 kg in Europe. Therapeutic drug monitoring may be beneficial for patients on combination therapy with RIF.





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Keywords: Efavirenz; HIV infection; pharmacokinetic interaction; rifampicin

Document Type: Research Article

Affiliations: Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy.

Publication date: May 1, 2007

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  • Current HIV Research aims to cover all the latest and outstanding developments of HIV research. We invite comprehensive review articles and novel, pioneering work in the basic and clinical fields on all areas of HIV research, including virus replication and gene expression, HIV assembly, virus-cell interaction, viral pathogenesis, epidemiology and transmission, anti-retroviral therapy and adherence, drug discovery, the latest developments in HIV/AIDS vaccines and animal models, mechanisms and interactions with AIDS related diseases, social and public health issues related to HIV disease, and prevention of viral infection. Each issue of the journal contains a series of timely in-depth reviews and original research written by leaders in the field covering a range of current topics on HIV research. Periodically, the journal will invite guest editors to devote an issue on a particular area of HIV research of great interest that increases our understanding of the virus and its complex interaction with the host.
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