Sim Ing-Kye, Davis Timothy M E, Ilett Kenneth F
Medicine Unit Fremantle, M510, School of Medicine and Pharmacology, University of Western Australia, Crawley 6009, Australia.
Antimicrob Agents Chemother. 2005 Jun;49(6):2407-11. doi: 10.1128/AAC.49.6.2407-2411.2005.
Piperaquine (PQ) is an antimalarial drug whose high lipid solubility suggests that its absorption can be increased by a high-fat meal. We examined the pharmacokinetics of PQ phosphate (500 mg given orally) in the fasting state and after a high-fat meal in eight healthy Caucasian volunteers (randomized crossover). Plasma PQ concentration-time profiles were analyzed by using noncompartmental pharmacokinetic analysis. In the fed state, the geometric mean Cmax increased by 213%, from 21.0 to 65.8 microg/liter (P<0.001). The time of Cmax was not significantly different between the fasting and fed states. The geometric mean area under the concentration-time curve from zero onward (AUC0-infinity) increased by 98%, from 3,724 to 7,362 microg h/liter (P=0.006). The oral bioavailability of PQ relative to the fasting state was 121% greater after the high-fat meal (95% confidence interval, 26 to 216% increase; P=0.020). The side effects, postural blood pressure changes, electrocardiographic corrected QT interval, serum glucose, and other biochemical and hematological indices were similar in the fasting and fed states over 28 days of follow-up.
哌喹（PQ）是一种抗疟药物，其高脂溶性表明高脂餐可增加其吸收。我们在8名健康的白种志愿者中（随机交叉）研究了空腹状态下和高脂餐后口服磷酸哌喹（500毫克）的药代动力学。采用非房室药代动力学分析方法分析血浆哌喹浓度-时间曲线。在进食状态下，几何平均Cmax增加了213%，从21.0微克/升增至65.8微克/升（P<0.001）。空腹和进食状态下Cmax出现的时间无显著差异。从0时起浓度-时间曲线下的几何平均面积（AUC0-∞）增加了98%，从3724微克·小时/升增至7362微克·小时/升（P=0.006）。高脂餐后哌喹相对于空腹状态的口服生物利用度提高了121%（95%置信区间，增加26%至本信息由辽宁省朝阳市中心医院药剂科副主任药师赵志刚提供。216%；P=0.020）。在28天的随访中，空腹和进食状态下的副作用、体位性血压变化、心电图校正QT间期、血糖以及其他生化和血液学指标相似。
