Beckmann J, Elsässer W, Gundert-Remy U, Hertrampf R
Abteilung für experimentelle und klinische Pharmakologie, Institut für Arzneimittel, BGA, West Berlin.
Eur J Clin Pharmacol. 1987;33(3):227-30. doi: 10.1007/BF00637553.
The mechanism of the theophylline-enoxacin interaction has been studied in six healthy subjects. Theophylline 250 mg was administered p.o., twice daily for 11 days in a sustained release dosage form. On the 4th day of treatment, blood samples were taken every 2 h and urine was collected over 1 dose interval. From Days 5 to 11 coated tablets of enoxacin 400 mg b.i.d. were coadministered. On Day 11 blood and urine were collected as on Day 4. The mean plasma theophylline concentration rose from 4.4 to 15.1 mg/l, corresponding to a 73.6% reduction in total clearance. The urinary excretion of unchanged theophylline increased from 12.7 to 35.3%, whereas the production of metabolites was reduced (1-demethylation 81.4%; 3-demethylation 83.1%, 8-hydroxylation 74.6%). The results indicate that the theophylline-enoxacin interaction may be due to inhibition of the cytochrome P-450 isozymes responsible for theophylline metabolism. Unexpectedly, the renal clearance of theophylline metabolites was found to be drastically reduced when enoxacin was coadministered. This led to unchanged or even to elevated plasma levels of the metabolites. The mechanism of this interaction is still to be elucidated, but it may be due to competition for renal tubular secretion.
已在6名健康受试者中研究了茶碱与依诺沙星的相互作用机制。以缓释剂型口服给予250毫克茶碱，每日两次，持续11天。在治疗的第4天，每2小时采集血样，并在1个剂量间隔内收集尿液。从第5天至第11天，联用400毫克依诺沙星的包衣片，每日两次。在第11天，像在第4天一样采集血样和尿液。茶碱的平均血浆浓度从4.4毫克/升升至15.1毫克/升，相应地总清除率降低了73.6%。未改变的茶碱的尿排泄量从12.7%增至35.3%，而代谢物的生成减少（N-1去甲基化81.4%；N-3去甲基化83.1%，8-羟基化74.6%）。结果表明，茶碱-依诺沙星相互作用可能是由于负责茶碱代谢的细胞色素P-450同工酶受到抑制。出乎意料的是，当联用依诺沙星时，发现茶碱代谢物的肾清除率大幅降低。这导致代谢物的血浆水平未改变甚至升高。这种相互作用的机制仍有待阐明，但可能是由于肾小管分泌的竞争所致。
