Ribera E, Pou L, Lopez R M, Crespo M, Falco V, Ocaña I, Ruiz I, Pahissa A
Infectious Disease Service, Clinical Biochemistry Service, Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain.
J Acquir Immune Defic Syndr. 2001 Dec 15;28(5):450-3. doi: 10.1097/00042560-200112150-00007.
To determine whether rifampicin reduces serum concentrations of nevirapine and whether nevirapine modifies serum concentrations of rifampicin, levels of these agents were determined at steady state by high-performance liquid chromatography in 10 HIV-infected patients with tuberculosis. The median area under the curve (AUC) 0-12h of nevirapine before and after rifampicin was 56.2 and 32.8 microg/ml per hour, respectively ( p =.04). This represents a 31% reduction in serum nevirapine concentrations. The C(max) decreased from 5.6 to 4.5 microg/ml ( p =.04), which represented a 36% reduction. A 21% decrease in the C(min) was not statistically significant. Exposure to rifampicin did not significantly differ between those patients who were receiving and were not receiving nevirapine. However, our study shows that rifampicin reduces serum exposure to nevirapine. The clinical implications for this reduction remain to be established. Given that the lowest trough serum concentration of nevirapine exceeded by more than 40 times the protein binding adjusted median infective dose (IC(50)) of wild-type HIV in all patients, we suggest that there is no need to increase nevirapine dosage when it is given with rifampicin.
为了确定利福平是否会降低奈韦拉平的血清浓度，以及奈韦拉平是否会改变利福平的血清浓度，我们通过高效液相色谱法对10例合并结核病的HIV感染患者在稳态时这些药物的水平进行了测定。利福平使用前后奈韦拉平的0至12小时曲线下面积（AUC）中位数分别为56.2和32.8微克/毫升·小时（p = 0.04）。这表明血清中奈韦拉平浓度降低了31%。最大血药浓度（C(max)）从5.6微克/毫升降至4.5微克/毫升（p = 0.04），降幅为36%。最小血药浓度（C(min)）降低21%，差异无统计学意义。接受和未接受奈韦拉平的患者中利福平的暴露量无显著差异。然而，我们的研究表明利福平会降低血清中奈韦拉平的暴露量。这种降低的临床意义仍有待确定。鉴于所有患者中奈韦拉平的最低谷浓度超过野生型HIV蛋白结合调整后的中位感染剂量（IC(50)）40多倍，我们建议奈韦拉平与利福平联用时无需增加剂量。
