Milavetz G, Vaughan L M, Weinberger M M
Clin Pharmacol Ther. 1987 Apr;41(4):388-91. doi: 10.1038/clpt.1987.46.
The elimination rate for theophylline varies greatly among patients, but recommendations for maintenance dosing schedules have assumed relatively little intrapatient variability even over extended time periods. Reports of large intrapatient variability of theophylline elimination rate and consequent clearance raise concerns regarding this assumption and also challenge the practice of assuming relative constancy of elimination rate in the performance of bioavailability studies of slow-release formulations. We therefore systematically studied under controlled conditions the elimination rate of theophylline in 10 patients over an extended time interval. The initial elimination rate constants ranged from 0.062 to 0.136 hours-1. The changes ranged from -5.9% to 9.4% of the initial value during intervals of 2 to 11 months. Correlation of the first and second values was 0.96. Thus the elimination rate of theophylline generally appears to vary little within individuals over time when studied under controlled conditions.
茶碱的消除率在患者之间差异很大，但维持给药方案的建议即使在较长时间段内也假定患者体内的变异性相对较小。关于茶碱消除率和随之而来的清除率在患者体内存在较大变异性的报告引发了对这一假设的担忧，同时也对在缓释制剂生物利用度研究中假设消除率相对恒定的做法提出了挑战。因此，我们在受控条件下系统地研究了10名患者在较长时间间隔内茶碱的消除率。初始消除速率常数范围为0.062至0.136小时-1。在2至11个月的间隔期间，变化范围为初始值的-5.9%至9.4%。第一个值和第二个值的相关性为0.96。因此，在受控条件下进行研究时，茶碱的消除率在个体内随时间推移通常变化很小。
