Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand.
Antimicrob Agents Chemother. 2011 Sep;55(9):3971-6. doi: 10.1128/AAC.00279-11. Epub 2011 Jun 27.
Dihydroartemisinin-piperaquine is a new, highly effective, and well-tolerated combination treatment for uncomplicated falciparum malaria. The lipophilic characteristic of piperaquine suggests that administration together with fat will increase the oral bioavailability of the drug, and this has been reported for healthy volunteers. This pharmacokinetic study monitored 30 adult patients with uncomplicated falciparum malaria for 4.5 months to evaluate the effects of the concomitant intake of fat on the total piperaquine exposure. The fixed-drug combination of dihydroartemisinin-piperaquine was given with water to fasting patients (n = 15) or was coadministered with 200 ml milk containing 6.4 g fat (n = 15). The drug combination was generally well tolerated, and there were no severe adverse effects reported for either group during the study. Total piperaquine exposure (area under the concentration-time curve from zero to infinity [AUC(0-∞)]; results are given as medians [ranges]) were not statistically different between fed (29.5 h · μg/ml [20.6 to 58.7 h · μg/ml]) and fasting (23.9 h · μg/ml [11.9 to 72.9 h · μg/ml]) patients, but the interindividual variation was reduced in the fed group. Overall, none of the pharmacokinetic parameters differed statistically between the groups. Total piperaquine exposure correlated well with the day 7 concentrations in the fasted group, but the fed group showed a poor correlation. In conclusion, the coadministration of 6.4 g fat did not have any significant effect on piperaquine pharmacokinetics in the treatment of uncomplicated malaria.
双氢青蒿素-哌喹是一种新的、高效且耐受性良好的复方药物，用于治疗无并发症的恶性疟。哌喹具有亲脂性，提示与脂肪一起给药将增加药物的口服生物利用度，这在健康志愿者中已有报道。这项药代动力学研究对 30 例无并发症的恶性疟成年患者进行了 4.5 个月的监测，以评估同时摄入脂肪对总哌喹暴露的影响。双氢青蒿素-哌喹固定剂量复方制剂与水一起空腹给药（n = 15）或与含有 6.4 g 脂肪的 200 ml 牛奶同时给药（n = 15）。该药物联合治疗通常具有良好的耐受性，在研究期间，两组均未报告严重不良事件。两组患者的总哌喹暴露量（从 0 到无穷大的浓度-时间曲线下面积[AUC(0-∞)]；结果以中位数[范围]表示）无统计学差异，进食组为 29.5 h·μg/ml[20.6 至 58.7 h·μg/ml]，禁食组为 23.9 h·μg/ml[11.9 至 72.9 h·μg/ml]，但进食组个体间变异减小。总体而言，两组间的药代动力学参数均无统计学差异。总哌喹暴露与禁食组第 7 天的浓度密切相关，但进食组的相关性较差。结论：在治疗无并发症疟疾时，6.4 g 脂肪的联合给药对哌喹的药代动力学没有显著影响。
