Fuhr U, Maier A, Keller A, Steinijans V W, Sauter R, Staib A H
Department of Clinical Pharmacology, University Hospital Frankfurt am Main, Germany.
Int J Clin Pharmacol Ther. 1995 Jun;33(6):311-4.
Grapefruit juice inhibits the biotransformation of several drugs, including caffeine (23% clearance reduction), which is metabolized by the cytochrome P450 isoform CYP1A2. Since CYP1A2 also participates in theophylline biotransformation, a randomized change-over study on a possible interaction between grapefruit juice and theophylline was conducted. Twelve healthy young male nonsmokers were included (median 26 (range 23-30) years, weight 73 (65-85) kg). Theophylline was given as a single dose of 200 mg in solution (Euphyllin 200), diluted by 100 ml of either water or grapefruit juice (751 mg/l naringin). Subsequently, additional fractionated 0.91 of water or juice were administered until 16 hours postdose. Theophylline concentrations in plasma withdrawn up to 24 hours postdose were measured by HPLC, and its pharmacokinetics were estimated using compartment model independent methods. To compare between the 2 treatments, ANOVA based point estimates and 90% confidence intervals (given in parentheses) were calculated for the test (= grapefruit coadministration) to reference (= water coadministration) ratios (Tmax: differences). These were: Cmax 0.90 (0.81-1.00), AUC 1.02 (0.95-1.11), Cmax/AUC 0.88 (0.81-0.95), T 1/2el 1.03 (0.98-1.09), Tmax 0.15 h (-0.11h-0.41 h). Thus, no pharmacokinetic interaction between grapefruit juice and theophylline was observed. This finding is in contrast to the effect of grapefruit juice reported on caffeine metabolism and may be due to the contribution of enzymes other than CYP1A2 to primary theophylline metabolism or to differences in naringin and/or naringenin kinetics between studies.
葡萄柚汁会抑制包括咖啡因（清除率降低23%）在内的多种药物的生物转化，咖啡因由细胞色素P450同工酶CYP1A2代谢。由于CYP1A2也参与茶碱的生物转化，因此开展了一项关于葡萄柚汁与茶碱之间可能存在相互作用的随机交叉研究。研究纳入了12名健康的年轻男性非吸烟者（年龄中位数26岁（范围23 - 30岁），体重73千克（65 - 85千克））。给予受试者单剂量200毫克的茶碱溶液（优菲林200），用100毫升水或葡萄柚汁（柚皮苷含量751毫克/升）稀释。随后，在给药后16小时内额外分次给予0.91份的水或果汁。通过高效液相色谱法测定给药后24小时内采集的血浆中茶碱浓度，并使用非房室模型独立方法估算其药代动力学。为比较两种治疗方法，计算了基于方差分析的点估计值和90%置信区间（括号内给出），用于测试（= 与葡萄柚汁合用）与对照（= 与水合用）的比率（Tmax：差异）。这些值分别为：Cmax 0.90（0.81 - 1.00），AUC 1.02（0.95 - 1.11），Cmax/AUC 0.88（0.81 - 0.95），T 1/2el 1.03（0.98 - 1.09），Tmax 0.15小时（-0.11小时 - 0.41小时）。因此，未观察到葡萄柚汁与茶碱之间存在药代动力学相互作用。这一发现与葡萄柚汁对咖啡因代谢的影响相反，可能是由于除CYP1A2之外的酶对茶碱初级代谢有贡献，或者是由于不同研究中柚皮苷和/或柚皮素动力学存在差异。
