Response to "Antiretroviral Therapy With Efavirenz in HIV-Infected Pregnant Women: Understanding the Possible Mechanisms for Drug-Drug Interaction".
Response to "Antiretroviral Therapy With Efavirenz in HIV-Infected Pregnant Women: Understanding the Possible Mechanisms for Drug-Drug Interaction".
复制标题
对“艾滋病毒感染孕妇的依非韦伦抗逆转录病毒治疗：了解药物相互作用的可能机制”的回应。
DOI：
10.1002/cpt.963
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发表时间：
2018
影响因子：
6.7
通讯作者：
Aweeka,FrancescaT
中科院分区：
文献类型：
--
作者：
Jagannathan,Prasanna;Kajubi,Richard;Aweeka,FrancescaT
We appreciate the letter by Dr. Srinivas (1) suggesting potential mechanisms by which dihydroartemisinin (DHA) and piperaquine (PQ) exposure were reduced in HIV-infected pregnant women receiving efavirenz (compared with HIV-uninfected pregnant women not receiving efavirenz). Dr. Srinivas argues that DHA bioavailability may be reduced due to efavirenz promoting intestinal presystemic glucuronidation of DHA to its glucuronide metabolite, thereby reducing the oral bioavailability and exposure of DHA without affecting its elimination. We agree that this certainly is plausible in spite of others reporting efavirenz does not impact intestinal metabolism (2, 3). We completed a study of bedaquiline, an antitubercular agent, in the absence and presence of efavirenz where the alterations of metabolite formation and elimination that we observed was perhaps best explained by efavirenz induction of metabolism within the gastrointestinal tract (presystemic) as well as the liver. Even though the peak levels of parent drug did not change, the elimination of the metabolite was faster than parent drug (ie did not follow the elimination slope of parent drug) and thus must have been formed before the parent drug reached the central plasma compartment (4).We also agree with Dr. Srinivas that induction of CYP3A4 by efavirenz may also influence PQ clearance, thereby leading to a reduced PQ half-life (5). This can most easily be explained by an induction of hepatic metabolism which has clearly been demonstrated for efavirenz (3).
