EFFECT OF GARLIC ON PHARMACOKINETICS OF SAQUINAVIR

大蒜对沙奎那韦药代动力学的影响

• 批准号: 6414325
• 负责人: STEPHEN PISCITELLI
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6414325
• 关键词: alternative medicine; clinical research; drug interactions; human subject; medicinal plants; nutrition related tag; pharmacokinetics; plant extracts; saquinavir

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.

艾滋病毒感染者广泛使用补充和替代药物。最近的数据显示，某些补充药物和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，有资料表明其对细胞色素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（saquinavir， SQV）的影响，10名健康受试者将单独接受SQV （Fortovase）治疗，并与一种非处方大蒜制剂联合使用。SQV最初将以1200mg TID的剂量单独给药3天，并在第4天早晨给药后收集一系列样品以测定SQV的药代动力学。从第5天开始，大蒜将作为一粒TID胶囊服用21天。在第22天（大蒜的第18天），沙奎那韦将再次以1200mg TID开始并持续三天。在研究第25天的早晨，受试者将接受最后一剂大蒜，并在收集系列样品时给予一剂沙奎那韦。然后将有10天的无药物洗脱期，之后将再次给予SQV三天。将于第四天上午采集样本，评估大蒜的抵消效果。血浆中SQV浓度将使用有效的高效液相色谱法测定。在大蒜存在和不存在的情况下，将确定SQV的稳态非室室参数。药代动力学参数将使用方差分析进行比较，方差分析将包括周期效应和治疗效果的因素。统计分析将包括计算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%的置信区间。这项研究将有助于确定艾滋病毒感染患者补充和替代疗法的药物相互作用潜力。