The effect of water-soluble vitamin E On cyclosporine pharmacokinetics in healthy volunteers

被引:107
作者
Chang, T
Benet, LZ
Hebert, MF
机构
[1] UNIV CALIF SAN FRANCISCO, DEPT PHARM, SAN FRANCISCO, CA 94143 USA
[2] UNIV CALIF SAN FRANCISCO, DIV CLIN PHARM, SAN FRANCISCO, CA 94143 USA
关键词
D O I
10.1016/S0009-9236(96)80007-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We evaluated the effect of water-soluble vitamin E (d-alpha-tocopheryl polyethylene glycol 1000 succinate [TPGS]; Liqui-E) on the oral pharmacokinetics of the cyclosporine, a poorly available (similar to 30%) drug, in healthy volunteers. Ten healthy subjects were given two doses of oral cyclosporine (10 mg/kg) separated by a 7-day washout period, Oral TGS (2.6 IU/kg) was administered concomitantly with one of the cyclosporine doses in a randomized order, A significant increase was observed in area under the blood concentration-time curve (AUC;mean +/- SD) with concomitant TPGS administration (3908 +/- 2601 versus 6296 +/- 5102 . hr/ml). Significant decreases were observed in apparent oral clearance (0.24 +/- 0.14 versus 0.15 +/- 0.08 L/hr/kg) and apparent oral steady-state volume of distribution (1.57 +/- 0.95 versus 1.07 +/- 0.73 L/kg), No significant changes were observed in the ratios of metabolites to parent drug AUC values, The comparable relative decreases in apparent oral clearance (38%) and apparent oral steady-state volume of distribution (30%) with TPGS are most likely explained by enhanced absorption, decreased counter transport back into the intestine by P-glycoprotein, or some unknown mechanism by which cyclosporine is protected from metabolism in the gut, thereby increasing bioavailability.
引用
收藏
页码:297 / 303
页数:7
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