EFFECT OF GARLIC ON PHARMACOKINETICS OF SAQUINAVIR

在感染艾滋病毒的人群中广泛使用补充和替代药物。最近的数据表明，某些补充药物与蛋白酶抑制剂之间存在严重的药物相互作用。大蒜是一种常用的膳食补充剂，有数据表明它对细胞色素P4503A4具有单剂量抑制作用和多剂量诱导作用。为了评估大蒜对蛋白酶抑制剂沙奎那韦(SQV)的影响，10名健康受试者将单独服用SQV(Fortovase)，并与非处方药大蒜制剂联合服用。SQV最初将以1200 mg，tid的剂量单独给药，连续3天，在第4天早上给药后，将采集系列样品用于SQV的药代动力学测定。从第5天开始，大蒜将作为一个胶囊，tid，共21天。在第22天(大蒜第18天)，沙奎那韦将再次开始，1200 mg，tid，持续3天。在学习第25天的早上，受试者将收到他们的最后一剂大蒜，并将在收集系列样本的同时服用一剂沙奎那韦。然后将有10天的洗脱期，没有药物，之后将再次给予SQV，为期3天。第四天上午将采集样本，以评估大蒜的抵消效果。血浆中的SQV浓度将使用经过验证的高效液相色谱方法进行测定。在大蒜存在和不存在的情况下，将确定SQV的稳态非隔室参数。药代动力学参数将使用方差分析进行比较，该方差分析将包括周期效应和治疗效应的因素。统计分析将包括计算在治疗阶段与单独使用沙奎那韦相比的AUC的平均比率，并确定95%的可信区间。这项研究将有助于确定HIV感染患者的补充和替代疗法的药物相互作用潜力。

Complementary and alternative medicines are widely used in the HIV-infected population. Recent data have shown serious drug interactions between certain complementary medicines and protease inhibitors. Garlic is a commonly used dietary supplement, and data are available suggesting that it has single-dose inhibitory effects and multiple-dose inducing effects on cytochrome P4503A4. To evaluate the effect of garlic on the protease inhibitor saquinavir (SQV), ten healthy subjects will receive SQV (Fortovase) alone and in combination with an over-the-counter garlic preparation. SQV initially will be administered alone at a dose of 1200 mg TID for three days, and serial samples will be collected for determination of SQV pharmacokinetics after the morning dose on day 4. Beginning on day 5, garlic will be administered as one capsule TID for 21 days. On day 22 (day 18 of garlic), saquinavir will be started again at 1200 mg TID and continued for three days. On the morning of study day 25, subjects will receive their last dose of garlic and will be administered a dose of saquinavir with collection of serial samples. There will then be a 10-day washout period with no drugs, after which SQV will be given again for three days. Samples will be collected on the morning of the fourth day to evaluate the offset of the effects of garlic. SQV concentrations in plasma will be determined using a validated HPLC method. Steady-state noncompartmental parameters of SQV in the presence and absence of garlic will be determined. Pharmacokinetic parameters will be compared using an ANOVA that will include factors for a period effect and a treatment effect. Statistical analyses will include calculation of the mean ratio of the AUC in the treatment phases compared with saquinavir alone and determination of 95 percent confidence intervals. This study will help define the drug interaction potential of complementary and alternative therapies in HIV-infected patients.