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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.

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



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.


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.


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.


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.

[Indexed for MEDLINE]

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