Ramachandran Geetha, Hemanthkumar Agibothu K, Rajasekaran Sigamani, Padmapriyadarsini Chandrasekaran, Narendran Gopalan, Sukumar Baluswamy, Sathishnarayan Srinivasan, Raja Krishnaraj, Kumaraswami Vasanthapuram, Swaminathan Soumya
HIV/AIDS Division, Tuberculosis Research Centre (Indian Council of Medical Research), Chennai, India.
J Acquir Immune Defic Syndr. 2006 May;42(1):36-41. doi: 10.1097/01.qai.0000214808.75594.73.
We studied the effect of rifampicin on steady-state pharmacokinetics of nevirapine and the impact of increasing the dose of nevirapine on its peak (Cmax) and trough (Cmin) levels in 13 HIV-infected patients on regular antiretroviral treatment with nevirapine-containing regimens (200 mg twice daily). A baseline pharmacokinetic study was conducted and repeated after 1 week of daily rifampicin (450/600 mg). The study was repeated in 7 of 8 patients who had subtherapeutic Cmin nevirapine levels after increasing nevirapine dose to 300 mg twice daily. Liver function was monitored. Rifampicin caused significant reductions in Cmax (42%), Cmin (53%), and exposure (46%) of nevirapine (P <.01). The Cmin of nevirapine fell below the therapeutic range of 3 microg/ml in 8 of 13 patients. An increase of nevirapine to 300 mg twice daily raised Cmin to therapeutic range in all 7 patients without exceeding the toxic level of 12 microg/mL. There were no clinical or laboratory adverse events. Our findings suggest that decreased bioavailability of nevirapine because of rifampicin coadministration could be overcome by increasing the dose of nevirapine from 200 to 300 mg twice daily without short-term adverse events. Further studies to evaluate the long-term safety of higher dose of nevirapine are required.
我们研究了利福平对奈韦拉平稳态药代动力学的影响，以及在13例接受含奈韦拉平方案（每日两次，每次200mg）常规抗逆转录病毒治疗的HIV感染患者中，增加奈韦拉平剂量对其峰浓度（Cmax）和谷浓度（Cmin）的影响。进行了一项基线药代动力学研究，并在每日服用利福平（450/600mg）1周后重复进行。在8例将奈韦拉平剂量增加至每日两次，每次300mg后Cmin低于治疗水平的患者中，对其中7例重复了该研究。监测肝功能。利福平使奈韦拉平的Cmax（42%）、Cmin（53%）和暴露量（46%）显著降低（P<.01）。13例患者中有8例奈韦拉平的Cmin降至3μg/ml的治疗范围以下。将奈韦拉平剂量增加至每日两次，每次300mg后，所有7例患者的Cmin均升至治疗范围，且未超过12μg/mL的毒性水平。未出现临床或实验室不良事件。我们的研究结果表明，每日两次将奈韦拉平剂量从200mg增加至300mg，可克服因联合使用利福平导致的奈韦拉平生物利用度降低的问题，且无短期不良事件。需要进一步研究评估更高剂量奈韦拉平的长期安全性。
