Redolfi A, Borgogelli E, Lodola E
Eur J Clin Pharmacol. 1979 May 21;15(4):257-61. doi: 10.1007/BF00618514.
The blood level versus time curve for unchanged cimetidine after a 200 mg oral dose has been determined in 20 apparently healthy subjects, ranging from 22 to 84 years of age. A significant relationship between the area under the curve (AUC) and age was found (r = 0.81; P less than 0.001). The peak concentrations of cimetidine were significantly inversely related to body weight (r = -0.71; P less than 0.001). The age-related increase in bioavailability of oral cimetidine, as measured by AUC, was probably due to decreased total clearance of the drug, which resulted from the opposed changes (by themselves not significant) of distribution volume towards a decrease and of half-life towards an increase with age. Reduction in the standard oral dose of cimetidine by one third to one half should be feasible in the elderly without loss of efficacy, and it may be advisable in order to obviate extreme individual responses that may occur in this population.
对20名年龄在22至84岁之间的明显健康受试者口服200毫克西咪替丁后,测定了未变化的西咪替丁的血药浓度-时间曲线。发现曲线下面积(AUC)与年龄之间存在显著关系(r = 0.81;P小于0.001)。西咪替丁的峰浓度与体重呈显著负相关(r = -0.71;P小于0.001)。通过AUC测量,口服西咪替丁的生物利用度随年龄增加,这可能是由于药物的总清除率降低,这是由于分布容积随年龄下降(自身无显著变化)和半衰期随年龄增加(自身无显著变化)这两种相反变化所致。将西咪替丁的标准口服剂量减少三分之一至二分之一对老年人应是可行的,且不会降低疗效,为避免该人群中可能出现的极端个体反应,这样做可能是可取的。