期刊
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
卷 50, 期 5, 页码 439-443出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAI.0b013e31819c33a3
关键词
antiretroviral treatment; efavirenz; pediatric; pharmacokinetic drug-drug interaction; rifampicin; trough concentration
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 closes of efavirenz as part of antiretroviral treatment. Trough concentration (C-min) 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 C-min 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 C-min (<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 C-min <1 mg/L could result in the rapid emergence of efavirenz-resistant mutations and treatment failure.
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