Tan K K, Trull A K, Uttridge J A, Metcalfe S, Heyes C S, Facey S, Evans D B
Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, England.
Clin Pharmacol Ther. 1995 Apr;57(4):425-33. doi: 10.1016/0009-9236(95)90212-0.
To investigate the effect of dietary fat on the pharmacokinetics and pharmacodynamics of cyclosporine.
Sixteen stable kidney transplants recipients (mean age, 50.4 years; age range, 19 to 63 years; six women) who were maintained on oral cyclosporine therapy were randomized to receive a high- or low-fat diet for periods of 7 days in a balanced crossover study. The crossover was separated by a 7-day washout period, when the usual diet was followed. Oral cyclosporine was taken once daily with breakfast. Twenty-four-hour pharmacokinetic studies were conducted during each dietary period on day 6 after oral cyclosporine and on day 7 after a 3-hour intravenous cyclosporine infusion (30% of oral dose). Sequential blood samples were also taken after the oral dose on day 6 for lymphocyte transformation studies.
The mean breakfast fat intake and total daily fat intake were 6.5 and 5.5 times higher, respectively, during the high-fat diet than during the low-fat diet. The bioavailability and clearance of cyclosporine were found to be significantly higher during the high-fat diet (p = 0.02 and p = 0.01, respectively). As a consequence, the area under the blood concentration-time curve (AUC) after the oral dose was not significantly different between the two diets. There were no significant differences in concanavalin A-stimulated proliferation of peripheral blood lymphocytes between the high- and low-fat diets.
An increased fat content of food significantly increases cyclosporine bioavailability and clearance. However, this is unlikely to be of clinical importance during oral administration because the AUC and pharmacodynamics of cyclosporine are not affected significantly.
研究膳食脂肪对环孢素药代动力学和药效学的影响。
16名接受口服环孢素治疗的稳定肾移植受者（平均年龄50.4岁；年龄范围19至63岁；6名女性）在一项平衡交叉研究中被随机分为接受高脂肪或低脂肪饮食7天。交叉期之间有7天的洗脱期，期间遵循常规饮食。口服环孢素每日早餐时服用一次。在口服环孢素后第6天的每个饮食期以及静脉输注环孢素（口服剂量的30%）3小时后第7天进行24小时药代动力学研究。在第6天口服给药后还采集系列血样用于淋巴细胞转化研究。
高脂肪饮食期间早餐平均脂肪摄入量和每日总脂肪摄入量分别比低脂肪饮食期间高6.5倍和5.5倍。发现高脂肪饮食期间环孢素的生物利用度和清除率显著更高（分别为p = 0.02和p = 0.01）。因此，两种饮食之间口服给药后的血药浓度-时间曲线下面积（AUC）无显著差异。高脂肪和低脂肪饮食之间在伴刀豆球蛋白A刺激的外周血淋巴细胞增殖方面无显著差异。
食物中脂肪含量增加显著提高环孢素的生物利用度和清除率。然而，在口服给药期间这在临床上不太可能具有重要意义，因为环孢素的AUC和药效学未受到显著影响。
