Kim Myo-Kyoung, Nightingale Charles, Nicolau David
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut 06102, USA.
Clin Pharmacokinet. 2003;42(11):985-96. doi: 10.2165/00003088-200342110-00004.
Previous pharmacokinetic studies have shown that a number of the quinolones inhibit the metabolism of caffeine.
To evaluate the effect of sex on the interaction between two quinolones and caffeine.
Multiple-dose, double-blind, randomised, three-period crossover study.
Twelve male and twelve female healthy volunteers.
Subjects received by mouth either fleroxacin 400 mg once daily and caffeine 100 mg three times daily, ciprofloxacin 500 mg twice daily and caffeine 100 mg three times daily, or caffeine alone, for 3 days. Subjects received each of the other regimens after 12-day washout periods. Plasma and urine concentrations were determined by validated high-performance liquid chromatography procedures and the data were analysed by noncompartmental linear pharmacokinetic methods.
Analysis of the interaction by sex revealed that females showed a significant difference in caffeine pharmacokinetics in the presence of ciprofloxacin (area under the concentration-time curve [AUC], peak plasma concentration [C(max)], time to C(max) [t(max)] and apparent total body clearance [CL/F]) and fleroxacin (AUC and CL/F) when compared with males. Significant differences between sexes were also observed in the pharmacokinetics of ciprofloxacin (AUC, elimination rate constant [beta] and CL/F) and fleroxacin (C(max) and beta) in the presence of caffeine. However, these significant differences disappeared when AUC and C(max) were normalised to 70 kg bodyweight and CL/F was expressed as per kg bodyweight.
The effect of quinolones on the pharmacokinetics of caffeine, and the reciprocal effect, are different between the sexes, due in part to different bodyweights.
既往药代动力学研究表明，多种喹诺酮类药物可抑制咖啡因的代谢。
评估性别对两种喹诺酮类药物与咖啡因之间相互作用的影响。
多剂量、双盲、随机、三周期交叉研究。
12名男性和12名女性健康志愿者。
受试者口服以下药物，持续3天：每日一次400mg氟罗沙星及每日三次100mg咖啡因；每日两次500mg环丙沙星及每日三次100mg咖啡因；或仅服用咖啡因。在12天的洗脱期后，受试者接受其他每种治疗方案。通过经验证的高效液相色谱法测定血浆和尿液浓度，并采用非房室线性药代动力学方法分析数据。
按性别进行的相互作用分析显示，与男性相比，女性在服用环丙沙星（浓度-时间曲线下面积[AUC]、血浆峰浓度[C(max)]、达峰时间[t(max)]和表观总体清除率[CL/F]）和氟罗沙星（AUC和CL/F）时，咖啡因药代动力学存在显著差异。在服用咖啡因的情况下，环丙沙星（AUC、消除速率常数[beta]和CL/F）和氟罗沙星（C(max)和beta）的药代动力学在性别之间也观察到显著差异。然而，当AUC和C(max)按70kg体重进行标准化，且CL/F按每千克体重表示时，这些显著差异消失。
喹诺酮类药物对咖啡因药代动力学的影响以及相互作用在性别之间存在差异，部分原因是体重不同。
