Adebayo G I
Department of Pharmacology, College of Medicine, Lagos, Nigeria.
Biopharm Drug Dispos. 1989 Jan-Feb;10(1):77-85. doi: 10.1002/bdd.2510100109.
The disposition of theophylline was studied on four occasions in eight healthy adult males. The control mean theophylline half-life and clearance were 7.32 h and 0.86 ml min-1 kg-1, respectively. After 5 days pretreatment with placebo the corresponding values of 7.01 and 0.88 were not significantly different, as were those of 7.43 and 0.85 after 5 days pretreatment with ranitidine (1.2 g daily). Five days pretreatment with cimetidine (1.0 g daily) resulted in a significant 44.4 per cent rise in the mean theophylline half-life and a 36.1 per cent fall in clearance. The fall in clearance correlated positively (r = 0.9407) with the initial value. The volume of distribution did not change significantly throughout the study period. The fact that, at as large a dose as 1.2 g daily, ranitidine did not impair theophylline metabolism suggests that similar results reported earlier with therapeutic doses of 300 mg daily cannot be ascribed to the lower dose of ranitidine employed. It is also suggested that the risk of theophylline toxicity consequent on cimetidine coadministration will be more likely in individuals with initial high theophylline clearance.
对8名健康成年男性在4个不同时间段研究了茶碱的处置情况。对照情况下，茶碱的平均半衰期和清除率分别为7.32小时和0.86毫升/分钟/千克。用安慰剂预处理5天后，相应数值为7.01和0.88，无显著差异；用雷尼替丁（每日1.2克）预处理5天后，数值为7.43和0.85，也无显著差异。用西咪替丁（每日1.0克）预处理5天导致茶碱平均半衰期显著升高44.4%，清除率下降36.1%。清除率的下降与初始值呈正相关（r = 0.9407）。在整个研究期间，分布容积无显著变化。每日剂量高达1.2克时雷尼替丁并未损害茶碱代谢，这表明先前报道的每日300毫克治疗剂量时的类似结果不能归因于所使用的雷尼替丁剂量较低。还表明，在初始茶碱清除率较高的个体中，与西咪替丁合用导致茶碱中毒的风险更可能出现。
