Cohen I A, Johnson C E, Berardi R R, Hyneck M L, Achem S R
Ther Drug Monit. 1985;7(4):426-34.
Influences of cimetidine dose and age on the cimetidine-theophylline interaction were evaluated. Group Y consisted of nine young adults, aged 22-35 years, and Group O of nine elderly adults, aged 60-74 years. Each subject completed three study phases in this randomized crossover study. During Phase A, oral dosing of 5 mg/kg theophylline was followed by 14 serial blood samples drawn over 36 h. Phases B and C involved the same procedures, but with oral cimetidine treatment of either 200 or 300 mg every 6 h, respectively. Theophylline pharmacokinetic parameters for Group Y, Group O, and Groups Y + O were calculated. Analyses of variance (ANOVA) for crossover design were performed for each variable. Intragroup interphase ANOVA results were interpreted using multiple range tests (Tukey's Q). Comparisons between groups were performed using two-sided Student's t tests (alpha = 0.05). Within each phase, the area under the concentration-time curve (AUC), elimination half-life (t1/2 el), clearance (Clp), and volume of distribution (Vd) of theophylline for the elderly subjects were not significantly different from those of the younger adults. Mean changes in AUC, t1/2 el, and Clp between Phases A and B for both Groups Y and O were highly significant (29.2 vs. 40.4, 36.7 vs. 44.8, and 25.9 vs. 29.8%, respectively). Further significant changes in those parameters were associated with 1.2 g/day of cimetidine (Phase C). Alterations of theophylline pharmacokinetics by cimetidine appear to be dose-related and are of similar magnitude in elderly and young healthy adults.
评估了西咪替丁剂量和年龄对西咪替丁 - 茶碱相互作用的影响。Y组由9名年龄在22 - 35岁的年轻成年人组成，O组由9名年龄在60 - 74岁的老年人组成。在这项随机交叉研究中，每个受试者完成三个研究阶段。在A阶段，口服5mg/kg茶碱，随后在36小时内采集14份系列血样。B阶段和C阶段涉及相同的程序，但分别每6小时口服200或300mg西咪替丁进行治疗。计算了Y组、O组以及Y + O组的茶碱药代动力学参数。对每个变量进行交叉设计的方差分析（ANOVA）。组内相间ANOVA结果使用多重范围检验（Tukey's Q）进行解释。组间比较使用双侧学生t检验（α = 0.05）。在每个阶段内，老年受试者茶碱的浓度 - 时间曲线下面积（AUC）、消除半衰期（t1/2 el）、清除率（Clp）和分布容积（Vd）与年轻成年人相比无显著差异。Y组和O组在A阶段和B阶段之间AUC、t1/2 el和Clp的平均变化均高度显著（分别为29.2%对40.4%、36.7%对44.8%和25.9%对29.8%）。这些参数的进一步显著变化与1.2g/天的西咪替丁有关（C阶段）。西咪替丁对茶碱药代动力学的改变似乎与剂量相关，并且在老年和年轻健康成年人中幅度相似。
