Bachmann K, Sullivan T J, Mauro L S, Martin M, Jauregui L, Levine L
Center for Applied Pharmacology, University of Toledo, Ohio.
J Clin Pharmacol. 1992 May;32(5):476-82. doi: 10.1002/j.1552-4604.1992.tb03865.x.
The influence of usual regimens of the H2 blocking drugs, cimetidine, ranitidine, and nizatidine on the steady-state plasma concentrations and pharmacokinetic characteristics of theophylline was studied in seventeen patients with chronic obstructive pulmonary disease (COPD). Patients were dosed to steady-state with an oral, sustained-release formulation of theophylline given in therapeutic doses twice daily for 2 weeks. Over the next 4 weeks, each patient received a week-long regimen of each H2 blocker concomitantly with theophylline, and a week-long regimen of theophylline alone (control). At the end of each of the latter 4 weeks the steady-state pharmacokinetics of theophylline were assessed. Neither ranitidine nor nizatidine treatment altered the steady-state pharmacokinetics of theophylline relative to the control phase (i.e. no H2 blocker treatment). Values for theophylline C(ave), Cssmax, AUC0-12, and CLoral were significantly different during cimetidine treatment compared with all other treatments (ranitidine, nizatidine, and control). Cimetidine increased theophylline Cssmax, AUC0-12 and Cave by approximately 32%, and decreased theophylline oral clearance by approximately 23%. The authors conclude that cimetidine alters the steady-state pharmacokinetics of theophylline in COPD patients, whereas ranitidine and nizatidine are without effect.
在17例慢性阻塞性肺疾病（COPD）患者中，研究了H2阻滞剂西咪替丁、雷尼替丁和尼扎替丁的常规用药方案对茶碱稳态血药浓度及药代动力学特征的影响。患者口服治疗剂量的缓释茶碱制剂，每日2次，给药2周以达到稳态。在接下来的4周里，每位患者接受为期一周的每种H2阻滞剂与茶碱联用的方案，以及为期一周的仅使用茶碱的方案（对照）。在这4周中每一周结束时，评估茶碱的稳态药代动力学。与对照阶段（即未使用H2阻滞剂治疗）相比，雷尼替丁和尼扎替丁治疗均未改变茶碱的稳态药代动力学。与所有其他治疗（雷尼替丁、尼扎替丁和对照）相比，西咪替丁治疗期间茶碱的C(ave)、Cssmax,、AUC0-12和CLoral值有显著差异。西咪替丁使茶碱的Cssmax、AUC0-12和Cave增加约32%，并使茶碱的口服清除率降低约23%。作者得出结论，西咪替丁会改变COPD患者茶碱的稳态药代动力学，而雷尼替丁和尼扎替丁则无此作用。
