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J Acquir Immune Defic Syndr. 2009 Apr 15;50(5):439-43. doi: 10.1097/QAI.0b013e31819c33a3.

Effect of rifampicin on efavirenz pharmacokinetics in HIV-infected children with tuberculosis.

Author information

1
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.

Abstract

SETTING:

Rifampicin may reduce plasma efavirenz concentrations by inducing the expression of the cytochrome P450 2B6, which metabolizes efavirenz. However, there is no data in pediatric patient populations.

METHODS:

We measured plasma efavirenz concentrations in 15 children during and after rifampicin-based antitubercular treatment. They were receiving standard doses of efavirenz as part of antiretroviral treatment. Trough concentration (Cmin) was estimated by extrapolation of the log-linear concentration-time line to 24 hours after the previous dose.

RESULTS:

Wide interpatient variation and marked bimodality of efavirenz concentrations were observed. Efavirenz Cmin was not significantly different during vs. after antitubercular treatment (median 0.83 mg/L interquartile range 0.59-6.57 vs. median 0.86 mg/L interquartile range 0.61-3.56; P = 0.125). Nine (60%) and 8 (53%) children had subtherapeutic Cmin (<1 mg/L) during and after antitubercular treatment, respectively.

CONCLUSIONS:

Concomitant rifampicin-based antitubercular treatment was not an important determinant of efavirenz concentrations. The substantial proportion of participants with estimated Cmin <1 mg/L could result in the rapid emergence of efavirenz-resistant mutations and treatment failure.

PMID:
19223781
DOI:
10.1097/QAI.0b013e31819c33a3
[Indexed for MEDLINE]

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