Matteelli Alberto, Saleri Nuccia, Villani Paola, Bonkoungou Victor, Carvalho Anna Cristina C, Kouanda Seni, Sanou Marie J, Simporé Jacques, Monno Laura, Carosi Giampiero, Regazzi Mario, Dembele Mathurin
Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy.
J Acquir Immune Defic Syndr. 2009 Sep 1;52(1):64-9. doi: 10.1097/qai.0b013e3181b0328f.
Nevirapine (NVP) plasma levels are reduced in patients receiving rifampicin (RFM) for tuberculosis (TB) treatment. We determined variations over time of the pharmacokinetic parameters of NVP in patients who receive RFM.
HIV-1-infected patients with CD4+ T-lymphocyte count <or=100 cells per microliter and TB diagnosis received standard anti-TB therapy and a fixed-dose combination of stavudine, lamivudine, and NVP. Full NVP pharmacokinetic curves were calculated at 4 (T1) and 10 weeks (T2) of combined therapy and at 4 (T3) and 26 weeks after termination of anti-TB therapy.
In 16 enrolled subjects, the median value of the area under the curve of NVP was reduced by 25.6% at T1 compared with NVP alone (43.7 vs. 58.7 microg x mL(-1) x h(-1); P = 0.02). The reduction was only 7.5% at T2 (54.3 vs. 58.7 microg x mL(-1) x h(-1); P = 0.17). The median C trough was reduced of 19.5% at T1 compared with T3 (3.3 vs. 4.2 microg/mL; P = 0.02) and of 7.1% at T2 compared with T3 (3.9 vs. 4.2 microg/mL; P = 0.17). The proportion of subjects with C trough values <or=3 microg/mL was 31.2% (5 of 16), 40.0% (6 of 15), and 7.7% (1 of 13) at T1, T2, and T3, respectively.
The reduction of the area under the curve of NVP during concomitant RFM treatment substantially decreases over time.
接受利福平（RFM）治疗结核病（TB）的患者，奈韦拉平（NVP）的血浆水平会降低。我们测定了接受RFM治疗的患者中NVP药代动力学参数随时间的变化情况。
CD4 + T淋巴细胞计数≤100个/微升且确诊为TB的HIV-1感染患者接受标准抗结核治疗以及司他夫定、拉米夫定和NVP的固定剂量联合用药。在联合治疗的第4周（T1）和第10周（T2）以及抗结核治疗终止后的第4周（T3）和第26周计算完整的NVP药代动力学曲线。
在16名入组受试者中，与单独使用NVP相比，T1时NVP曲线下面积的中位数降低了25.6%（43.7对58.7微克·毫升-1·小时-1；P = 0.02）。T2时降低仅7.5%（54.3对58.7微克·毫升-1·小时-1；P = 0.17）。与T3相比，T1时C谷值中位数降低了19.5%（3.3对4.2微克/毫升；P = 0.02），T2时与T3相比降低了7.1%（3.9对4.2微克/毫升；P = 0.17）。C谷值≤3微克/毫升的受试者比例在T1、T2和T3时分别为31.2%（16名中的5名）、40.0%（15名中的6名）和7.7%（13名中的1名）。
在同时使用RFM治疗期间，NVP曲线下面积的降低会随着时间大幅减少。
