Rafi J A, Frazier L M, Driscoll-Bannister S M, O'Hara K A, Garnett W R, Pugh C B
School of Pharmacy, Virginia Commonwealth University, Richmond 23298, USA.
Ann Pharmacother. 1999 Jul-Aug;33(7-8):769-74. doi: 10.1345/aph.18314.
To determine the effects of the maximum recommended over-the-counter (OTC) cimetidine dosage on phenytoin concentrations in ambulatory seizure patients on long-term phenytoin therapy.
Adults with seizure disorders requiring phenytoin therapy were recruited. Trough total phenytoin concentrations were measured initially and once weekly for six weeks. All assays were performed using Biotrack patient-side cartridges. After a two-week baseline period, patients took cimetidine 200 mg twice daily for two weeks. Toxicity was monitored via weekly neurologic examinations and midweek telephone surveys. Patients were asked to return to clinic weekly during a two-week cimetidine washout period.
Nine patients entered and completed the study. All but two patients took other anticonvulsants known to interact with phenytoin (carbamazepine, n = 5; phenobarbital, n = 2). No adverse effects or changes in seizure frequency were reported. Paired Student's t-tests revealed no significant difference between serum phenytoin concentrations before (12.3+/-3.2 mg/L [mean +/- SD]) and after (12.8+/-4.0 mg/L) two weeks on the OTC cimetidine regimen. No differences were noted in estimated pharmacokinetic parameters (maximum metabolic rate, Michaelis-Menten constant) for the same time periods (paired Student's t-test, p > 0.05). The Biotrack assay had an r2 = 0.7311 (p < 0.001, two-sided) when compared with TDx.
It is possible that the lack of change in phenytoin concentrations was a result of the low daily dosage of cimetidine used or other factors related to the "real world" setting of the study. However, the potential for a serious drug interaction occurring in patients taking long-term oral phenytoin and OTC cimetidine appears to be small.
确定非处方（OTC）西咪替丁最大推荐剂量对长期接受苯妥英治疗的门诊癫痫患者苯妥英浓度的影响。
招募需要苯妥英治疗的癫痫症成年患者。最初测量苯妥英总谷浓度，并在六周内每周测量一次。所有检测均使用Biotrack患者端试剂盒进行。在为期两周的基线期后，患者每日两次服用200 mg西咪替丁，持续两周。通过每周的神经学检查和周中电话调查监测毒性。在为期两周的西咪替丁洗脱期，要求患者每周返回诊所。
9名患者进入并完成了研究。除两名患者外，所有患者都服用了其他已知与苯妥英相互作用的抗惊厥药（卡马西平，n = 5；苯巴比妥，n = 2）。未报告不良反应或癫痫发作频率变化。配对学生t检验显示，在OTC西咪替丁治疗方案两周前后，血清苯妥英浓度（12.3±3.2 mg/L [平均值±标准差]）与（12.8±4.0 mg/L）之间无显著差异。在相同时间段内，估计的药代动力学参数（最大代谢率、米氏常数）无差异（配对学生t检验，p>0.05）。与TDx相比，Biotrack检测的r2 = 0.7311（p<0.001，双侧）。
苯妥英浓度缺乏变化可能是由于所用西咪替丁的日剂量较低或与研究的“现实世界”环境相关的其他因素所致。然而，长期口服苯妥英和OTC西咪替丁的患者发生严重药物相互作用的可能性似乎较小。
