Jonkman J H, Upton R A
Clin Pharmacokinet. 1984 Jul-Aug;9(4):309-34. doi: 10.2165/00003088-198409040-00002.
Since up to 90% of a theophylline dose is biotransformed, drugs influencing microsomal enzyme systems in the liver may affect the elimination of theophylline. Other integrated mechanisms (e.g. hepatic uptake) may also be altered by concurrent administration of other drugs. Whatever the mechanism, the interaction may be sufficient to necessitate adjustment of the theophylline dosage, preferably guided by plasma theophylline determinations. Comedication with phenobarbitone may require an increase of the theophylline dose by about 30% due to increased clearance resulting from enzyme induction. Similarly, with phenytoin and carbamazepine a dose increase of about 40 to 50% may be required. In the case of rifampicin, isoniazid or sulphinpyrazone comedication, an increase of the theophylline dose by about 20 to 25% may be needed. On the other hand, other drugs decrease theophylline clearance, making a reduction in the dose of concurrent theophylline advisable: with usual doses of erythromycin, propranolol and isoprenaline (isoproterenol), a reduction of about 25% is needed; with cimetidine and oral contraceptives by about 30% or more; and with triacetyloleandomycin (troleandomycin) by about 50%. In high doses, the xanthine oxidase inhibitor allopurinol can also retard theophylline elimination, and a reduction of the theophylline dose by about 20% may be advisable. Conflicting results have been reported on the influence of frusemide (furosemide) and influenza vaccines, while data regarding the effect of corticosteroids, benzodiazepines and verapamil on theophylline kinetics are not yet conclusive. Many drugs, however, appear not to significantly affect theophylline clearance. Some are from the same therapeutic group as the drugs mentioned above and offer clinical alternatives for coadministration with theophylline. Examples of drugs not found to have a significant effect on theophylline pharmacokinetics are ranitidine, josamycin, midecamycin, amoxycillin, tetracycline, cephalexin, cefaclor, orciprenaline, metoprolol, antacids, medroxyprogesterone acetate, metoclopramide and metronidazole. Most of the drugs discussed in this review appear not to affect the volume of distribution of theophylline significantly.
由于高达90%的茶碱剂量会发生生物转化，影响肝脏微粒体酶系统的药物可能会影响茶碱的消除。其他整合机制（如肝脏摄取）也可能因同时服用其他药物而改变。无论机制如何，这种相互作用可能足以需要调整茶碱剂量，最好在血浆茶碱测定的指导下进行。与苯巴比妥合用可能需要将茶碱剂量增加约30%，因为酶诱导导致清除率增加。同样，与苯妥英和卡马西平合用可能需要将剂量增加约40%至50%。在与利福平、异烟肼或磺吡酮合用时，可能需要将茶碱剂量增加约20%至25%。另一方面，其他药物会降低茶碱清除率，因此建议减少同时服用的茶碱剂量：使用常规剂量的红霉素、普萘洛尔和异丙肾上腺素时，需要减少约25%；与西咪替丁和口服避孕药合用时减少约30%或更多；与三乙酰竹桃霉素合用时减少约50%。高剂量时，黄嘌呤氧化酶抑制剂别嘌醇也会延迟茶碱的消除，可能建议将茶碱剂量减少约20%。关于速尿（呋塞米）和流感疫苗的影响报道结果相互矛盾，而关于皮质类固醇、苯二氮䓬类药物和维拉帕米对茶碱动力学影响的数据尚未定论。然而，许多药物似乎对茶碱清除率没有显著影响。有些药物与上述药物属于同一治疗组，为与茶碱合用提供了临床替代方案。未发现对茶碱药代动力学有显著影响的药物有雷尼替丁、交沙霉素、麦迪霉素、阿莫西林、四环素、头孢氨苄、头孢克洛、奥西那林、美托洛尔、抗酸剂、醋酸甲羟孕酮、甲氧氯普胺和甲硝唑。本综述中讨论的大多数药物似乎对茶碱的分布容积没有显著影响。
