A Compartmental Pharmacokinetic Evaluation of Long-Acting Rilpivirine in HIV-Negative Volunteers for Pre-Exposure Prophylaxis
A Compartmental Pharmacokinetic Evaluation of Long-Acting Rilpivirine in HIV-Negative Volunteers for Pre-Exposure Prophylaxis
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DOI：
10.1038/clpt.2014.118
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发表时间：
2014-09-01
影响因子：
6.7
通讯作者：
Boffito, M.
中科院分区：
文献类型：
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作者：
Jackson, A. G. A.;Else, L. J.;Boffito, M.
长效阿匹韦林（RPV-LA）是一种胃肠外制剂，可延长血浆暴露时间。我们探索了单次给药后的多室药代动力学（PK），用于暴露前预防。入组了66名HIV阴性志愿者：女性接受300、600或1，200 mg肌内给药，测量给药后84天的血浆和生殖器水平;接受600 mg的男性在血浆和直肠中测定的PK相似。还评估了宫颈阴道灌洗（CVL）的离体抗病毒活性。单次给药后，RPV浓度在第6-8天达到峰值，并存在于血浆和生殖道液中至第84天。阴道和男性直肠组织中的水平与血浆中的水平相匹配。在1，200 mg剂量下，CVL在第28天和第56天显示出高于基线的更大抗病毒活性。所有剂量均耐受良好。所有剂量均延长了血浆和生殖道利匹韦林暴露。重复给药的PK和病毒抑制在进一步的剂量选择中将是重要的。
Rilpivirine long-acting (RPV-LA) is a parenteral formulation enabling prolonged plasma exposure. We explored its multiple-compartment pharmacokinetics (PK) after a single dose, for pre-exposure prophylaxis. Sixty-six HIV-negative volunteers were enrolled: women received an intramuscular dose of 300, 600, or 1,200 mg, with plasma and genital levels measured to 84 days postdose; men receiving 600 mg had similar PK determined in plasma and rectum. Ex vivo antiviral activity of cervicovaginal lavage (CVL) was also assessed. After a single dose, RPV concentrations peaked at days 6-8 and were present in plasma and genital-tract fluid to day 84. Vaginal and male rectal tissue levels matched those in plasma. At the 1,200 mg dose, CVL showed greater antiviral activity, above baseline, at days 28 and 56. All doses were well tolerated. All doses gave prolonged plasma and genital-tract rilpivirine exposure. PK and viral inhibition of repeated doses will be important in further dose selection.