THE EFFECT OF FOOD AND BILE-ACID ADMINISTRATION ON THE RELATIVE BIOAVAILABILITY OF CYCLOSPORINE
THE EFFECT OF FOOD AND BILE-ACID ADMINISTRATION ON THE RELATIVE BIOAVAILABILITY OF CYCLOSPORINE
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DOI：
10.1111/j.1365-2125.1990.tb03677.x
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发表时间：
1990-05-01
影响因子：
3.4
通讯作者：
DAHLQVIST, R
中科院分区：
文献类型：
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作者：
LINDHOLM, A;HENRICSSON, S;DAHLQVIST, R
1.在11名健康志愿者中，在三种不同的情况下单次口服环孢菌素胶囊后，研究了环孢菌素的相对生物利用度;空腹、早餐和早餐与胆汁酸片（400 mg胆汁酸和100 mg去氢胆汁酸））。2.与早餐和胆汁酸片同时服用时，环孢素血药浓度-时间曲线下面积（AUC）（9078 ng·ml ~（-1）h）显著高于早餐（7453 ng·ml ~（-1）h，P < 0.05）和空腹（7283 ng·ml ~（-1）h，P < 0.01）。3. 9/11例受试者在早餐或早餐胆汁酸片服用环孢素时，血药浓度-时间曲线呈现双峰，但在空腹服用环孢素时，血药浓度-时间曲线仅呈现一个峰，表明环孢素存在肠肝循环或餐后第二吸收相。4.在一项单独的研究中，在19名接受口服环孢素溶液（平均剂量2.0 mg kg-1，每日两次）治疗的临床稳定的门诊移植受者中，在胆汁酸治疗1周前后测量12 h血环孢素谷浓度。环孢菌素的给药在食物摄入方面不规范。胆汁酸治疗前后环孢素血药浓度无显著性差异（114 . ±. 38 ng ml-1 vs 121 . ±. 38 ng ml-1）。5. CyA的吸收是不完全和可变的，取决于几个因素，如胃排空，肠动力，胆汁组成和流量以及合并用药。得出结论，在严格标准化的条件下，口服胆汁酸补充剂将适度提高环孢素的吸收。
1. The relative bioavailability of cyclosporin was studied in 11 healthy volunteers after single oral capsule doses of cyclosporin on three separate occasions; fasting, with breakfast and with breakfast together with bile acid tablets (400 mg of cholic acid and 100 mg of dehydrocholic acid). 2. There was a significant increase in the area under the blood concentration vs time curve (AUC) of cyclosporin with the drug was taken together with breakfast and bile acid tablets (9078 ng ml-1 h) as compared with breakfast alone (7453 ng ml-1 h, P < 0.05) or fasting conditions (7283 ng ml-1 h, P < 0.01). 3. A blood drug concentration vs time curve displaying two peaks was present in 9/11 subjects when cyclosporin was taken with breakfast or with breakfast bile acid tablets, but only one peak was present when cyclosporin was taken during fasting, suggesting an enterohepatic circulation of cyclosporin or a second absorption phase after the meal. 4. In a separate study, 12 h trough blood cyclosporin concentrations were measured before and after 1 week of bile acid treatment in 19 clinically stable, out-patient transplant recipients who were treated with oral cyclosporin solution (mean dose 2.0 mg kg-1 twice daily). The administration of cyclosporin was not standardized with regard to food intake. There was no significant difference in the blood concentrations of cyclosporin before and after bile acid treatment (114 .+-. 38 ng ml-1 vs 121 .+-. 38 ng ml-1). 5. The absorption of CyA is incomplete and variable and depends on several factors such as gastric emptying, intestinal motility, bile composition and flow and concurrent medication. It is concluded that under strictly standardized conditions oral bile acid supplementation will moderately enhance cyclosporin absorption.