Bailey D G, Arnold J M, Munoz C, Spence J D
Victoria Hospital, University of Western Ontario, Canada.
Clin Pharmacol Ther. 1993 Jun;53(6):637-42. doi: 10.1038/clpt.1993.84.
Grapefruit juice produces a marked and variable increase in felodipine bioavailability. The pharmacokinetics of felodipine and its single primary oxidative metabolite, dehydrofelodipine, were studied after drug administration with 200 ml water, grapefruit juice, or naringin in water at the same concentration as the juice in a randomized crossover trial of nine healthy men. With grapefruit juice, mean +/- SEM felodipine area under the plasma concentration-time curve (AUC) and peak plasma concentration (Cmax) were 206% +/- 23% (range, 123% to 330%, p < 0.01) and 170% +/- 24% (range, 127% to 310%, p < 0.02), respectively, compared with water. Dehydrofelodipine/felodipine ratios for AUC (1.5 +/- 0.2 versus 2.2 +/- 0.2, p < 0.001) and felodipine Cmax (1.5 +/- 0.2 versus 2.2 +/- 0.2, p < 0.001) were reduced, consistent with inhibition of presystemic felodipine metabolism. Intersubject changes in felodipine and dehydrofelodipine AUC supported inhibition of both primary and secondary metabolic steps as a mechanism. The interaction could not be predicted from baseline pharmacokinetics with water and did not result in more consistent bioavailability among individuals. Naringin solution produced much less of an interaction, showing that other factors were important.
葡萄柚汁可使非洛地平的生物利用度显著且呈可变增加。在一项针对9名健康男性的随机交叉试验中，研究了非洛地平及其单一主要氧化代谢产物脱氢非洛地平在与200毫升水、葡萄柚汁或与葡萄柚汁浓度相同的柚皮苷水溶液同时给药后的药代动力学。与水相比，饮用葡萄柚汁后，非洛地平的血浆浓度-时间曲线下平均面积（AUC）和血浆峰浓度（Cmax）分别为206%±23%（范围为123%至330%，p<0.01）和170%±24%（范围为127%至310%，p<0.02）。AUC的脱氢非洛地平/非洛地平比值（1.5±0.2对2.2±0.2，p<0.001）和非洛地平Cmax的脱氢非洛地平/非洛地平比值（1.5±0.2对2.2±0.2，p<0.001）均降低，这与非洛地平的首过代谢受到抑制一致。非洛地平及脱氢非洛地平AUC的个体间变化支持将首过代谢和二级代谢步骤均受抑制作为一种机制。这种相互作用无法根据水的基线药代动力学进行预测，且并未使个体间的生物利用度更趋一致。柚皮苷溶液产生的相互作用要小得多，这表明其他因素也很重要。
