Dose-dependent elimination of theophylline in rats.
Dose-dependent elimination of theophylline in rats.
复制标题
大鼠中茶碱的剂量依赖性消除。
DOI：
10.3109/00498258509045346
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
D. Breimer
中科院分区：
文献类型：
--
作者：
M. Teunissen;I. Brorens;J. M. Geerlings;D. Breimer
本文研究了不同剂量茶碱对大鼠体内代谢速率的影响。在剂量为52或115 mg/kg后，初始浓度为2.5 mg/kg。根据一级过程衰变，表观半衰期约为4小时。然而，在4至8小时后，曲线的斜率下降，导致消除半衰期约为70分钟。在6或11 mg/kg剂量后也发现类似的半衰期为70分钟。AUC随剂量不成比例地增加，表明消除能力有限。在茶碱的两种主要代谢产物的容量限制消除中未观察到差异：形成的1，3-二甲基尿酸和1-甲基尿酸的量之间的比率与茶碱的剂量无关。较高剂量后最初的表观一级衰减是由容量有限的代谢和原型茶碱的代偿性利尿增加引起的。得出结论，茶碱在大鼠中的线性药代动力学仅适用于不超过10 mg/kg的剂量。
The effect of different doses on the rate of metabolism of theophylline in rats was investigated. After doses of 52 or 115 mg/kg, the initial concn. decayed according to a first-order process with an apparent half-life of about four hours. However, after four to eight hours the slope of the curves declined, resulting in elimination half-lives of about 70 min. Similar half-lives of 70 min were also found after doses of 6 or 11 mg/kg. The AUC increased disproportionately with dose, indicating capacity-limited elimination. No differences were observed in capacity-limited elimination of the two major metabolites of theophylline: the ratio between the amounts of 1,3-dimethyluric acid and 1-methyluric acid formed was independent of the dose of theophylline. The initial apparent first-order decay after higher doses resulted from a combination of capacity-limited metabolism and compensatory increased diuresis of unchanged theophylline. It is concluded that linear pharmacokinetics of theophylline in rats apply only to doses not exceeding 10 mg/kg.