Ducharme M P, Provenzano R, Dehoorne-Smith M, Edwards D J
Department of Pharmacy Practice, College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, MI 48202, USA.
Br J Clin Pharmacol. 1993 Nov;36(5):457-9. doi: 10.1111/j.1365-2125.1993.tb00395.x.
Components of grapefruit juice have been shown to inhibit CYP3A4 activity, the enzyme involved in cyclosporine metabolism. Eleven medically stable patients (seven males, four females) receiving cyclosporine following kidney transplantation were instructed to take their usual dose of cyclosporine with water for 1 week (Phase 1), with grapefruit juice (8 ounces) for 1 week (Phase 2) and again with water for 1 week (Phase 3). Trough blood samples were obtained at the end of each phase for measurement of cyclosporine concentration using a specific monoclonal whole blood radioimmunoassay. Cyclosporine trough concentrations averaged 116.9 +/- 51.6 ng ml(-1) in the first phase, 145.3 +/- 44.7 ng ml(-1) with grapefruit juice (P < 0.05 compared with the first and third phases) and 111.2 +/- 56.1 ng ml(-1) in the third phase. Cyclosporine concentrations increased in 8 of 11 patients when given with grapefruit juice (mean increase 32%; range -4 to 97%) and declined in 10 of 11 when subjects resumed taking cyclosporine with water (mean decrease 27%). These results suggest that grapefruit juice increases trough concentrations of cyclosporine in blood, possibly by inhibiting pre-hepatic gut wall metabolism, and could be useful in optimizing therapy with this drug.
葡萄柚汁的成分已被证明可抑制细胞色素P450 3A4（CYP3A4）的活性，该酶参与环孢素的代谢。11例肾移植后接受环孢素治疗且病情稳定的患者（7例男性，4例女性）被要求在1周内用水服用常规剂量的环孢素（第1阶段），在接下来的1周内用葡萄柚汁（8盎司）送服环孢素（第2阶段），然后再用水服用环孢素1周（第3阶段）。在每个阶段结束时采集血样，采用特异性单克隆全血放射免疫分析法测定环孢素浓度。环孢素谷浓度在第1阶段平均为116.9±51.6 ng/ml，在服用葡萄柚汁时为145.3±44.7 ng/ml（与第1阶段和第3阶段相比，P<0.05），在第3阶段为111.2±56.1 ng/ml。11例患者中有8例在服用葡萄柚汁时环孢素浓度升高（平均升高32%；范围为-4%至97%），11例患者中有10例在重新用水服用环孢素时浓度下降（平均下降27%）。这些结果表明，葡萄柚汁可能通过抑制肝前肠壁代谢来提高血液中环孢素的谷浓度，这可能有助于优化该药物的治疗效果。
