Carbó M, Segura J, De la Torre R, Badenas J M, Camí J
Department of Pharmacology and Toxicology, Institut Municipal d'Investigació Mèdica, Barcelona, Spain.
Clin Pharmacol Ther. 1989 Mar;45(3):234-40. doi: 10.1038/clpt.1989.23.
Six healthy volunteers received a single caffeine dose after pretreatment with norfloxacin, pipemidic acid, or placebo in a crossover, randomized, single-blind clinical trial. Quinolones altered the pharmacokinetics of caffeine, with a significant increase in the AUCs and a decrease in plasma clearance. The elimination half-life increased significantly with pipemidic acid. The apparent volume of distribution, mean renal clearance, and time to reach maximum caffeine concentrations remained unaltered. There was a decline in caffeine metabolite levels in the 24-hour urine samples for both quinolone treatments, suggesting that pipemidic acid and, to a lesser degree, norfloxacin inhibit metabolism of the N-demethylation pathways of caffeine. The practical consequence of this observation could be caffeine accumulation during repeated intake of coffee. In two additional healthy volunteers under a controlled multiple-dose regimen of caffeine ingestion, administration of pipemidic acid for 2 days caused a fourfold increase in the plasma concentrations of caffeine.
在一项交叉、随机、单盲临床试验中，六名健康志愿者在接受诺氟沙星、吡哌酸或安慰剂预处理后，接受了单次咖啡因剂量。喹诺酮类药物改变了咖啡因的药代动力学，AUC显著增加，血浆清除率降低。吡哌酸使消除半衰期显著延长。分布表观容积、平均肾清除率以及达到咖啡因最大浓度的时间保持不变。两种喹诺酮治疗的24小时尿液样本中咖啡因代谢物水平均下降，表明吡哌酸以及程度较轻的诺氟沙星抑制了咖啡因N-去甲基化途径的代谢。这一观察结果的实际后果可能是在反复摄入咖啡期间咖啡因积累。在另外两名接受咖啡因摄入控制多剂量方案的健康志愿者中，给予吡哌酸2天导致咖啡因血浆浓度增加了四倍。
