Rotger Margalida, Colombo Sara, Furrer Hansjakob, Décosterd Laurent, Buclin Thierry, Telenti Amalio
Institute of Microbiology, University Hospital, Lausanne, Switzerland.
Antivir Ther. 2007;12(1):115-8.
A recent report described a possible interaction between tenofovir (TFV) and efavirenz (EFV). Patients developed neuropsychiatric manifestations upon introduction of TFV on a stable EFV-containing regimen. We evaluated the possibility of a pharmacokinetic interaction between TFV and EFV by assessing cross-sectional and longitudinal data in 169 individuals receiving EFV.
EFV plasma area-under-the-curve (AUC) levels were comparable among individuals receiving (n=18) or not receiving TFV (n=151); 57,962 versus 52,293 ngh/ml. However, under conditions of limited EFV metabolism, that is, the group of 23 individuals carrying two copies of CYP2B6 loss/diminished-function alleles, plasma AUC values were highest among individuals receiving TFV (n=5, 353,031 ngh/ml), compared with those not receiving TFV (n=18, 180,689 ng*h/ml). Statistical analysis identified both a global, sixfold effect of CYP2B6 loss/diminished function (P < 0.0001) and a significant interaction between the number of loss/diminished-function alleles and the co-medication with TFV (P = 0.009).
Although there is no clear evidence for a pharmacokinetic interaction between TFV and EFV, we cannot rule out an interaction between these drugs restricted to individuals who are slow EFV metabolizers.
最近一份报告描述了替诺福韦（TFV）与依非韦伦（EFV）之间可能存在的相互作用。在稳定的含依非韦伦治疗方案中引入替诺福韦后，患者出现了神经精神症状。我们通过评估169例接受依非韦伦治疗的患者的横断面和纵向数据，来评估替诺福韦与依非韦伦之间药代动力学相互作用的可能性。
接受（n = 18）或未接受替诺福韦（n = 151）的个体中，依非韦伦的血浆曲线下面积（AUC）水平相当；分别为57,962和52,293 ngh/ml。然而，在依非韦伦代谢受限的情况下，即23例携带两个拷贝CYP2B6缺失/功能减退等位基因的个体中，接受替诺福韦的个体（n = 5，353,031 ngh/ml）的血浆AUC值高于未接受替诺福韦的个体（n = 18，180,689 ng*h/ml）。统计分析确定了CYP2B6缺失/功能减退的整体六倍效应（P < 0.0001）以及缺失/功能减退等位基因数量与替诺福韦联合用药之间的显著相互作用（P = 0.009）。
虽然没有明确证据表明替诺福韦与依非韦伦之间存在药代动力学相互作用，但我们不能排除这些药物在依非韦伦代谢缓慢个体中存在相互作用的可能性。
