Bruguerolle B, Valli M, Bouyard L, Jadot G, Bouyard P
Eur J Drug Metab Pharmacokinet. 1981;6(3):189-93. doi: 10.1007/BF03189488.
The purpose of the present study was to investigate whether the time of day (24 h) at which carbamazepine is administered influences its pharmacokinetics in the rat. The pharmacokinetics of a single, 100 mg . kg-1 bodyweight per os, dose of carbamazepine were studied at four different fixed time points of a 24-hour period (i.e. 10.00, 16.00, 22.00 or 04.00 h) in Wistar AF-SPF adult male rats maintained under controlled environmental conditions (LD: 18.00 - 06.00h) during October 1978. The total plasma levels and the unbound fraction were measured according to an immunoenzymatic method (EMIT). The effects of fasting were also investigated. The data shows circadian variations of pharmacokinetic parameters: the maximum peak concentration and the maximum time to reach this peak was observed when the drug was given respectively at 16.00h and at 10.00h. The elimination half-life varied from 15.15 hours at 16.00h to 10.48 hours at 22.00h. The observed variations may be related to: daily fluctuations of absorption or binding of the drug; diurnal variations of the hepatic drug metabolizing enzymes responsible for the inactivation; and/or diurnal variations in excretion rate of the drug.
本研究的目的是调查卡马西平给药的一天中的时间（24小时）是否会影响其在大鼠体内的药代动力学。在1978年10月，对处于可控环境条件（光照：18.00 - 06.00h）下的成年雄性Wistar AF - SPF大鼠，在24小时周期的四个不同固定时间点（即10.00、16.00、22.00或04.00h）研究了口服单剂量100mg·kg-1体重的卡马西平的药代动力学。根据免疫酶法（EMIT）测量总血浆水平和未结合分数。还研究了禁食的影响。数据显示药代动力学参数存在昼夜变化：分别在16.00h给药时观察到最大峰值浓度，在10.00h给药时观察到达到该峰值的最长时间。消除半衰期从16.00h的15.15小时变化到22.00h的10.48小时。观察到的变化可能与以下因素有关：药物吸收或结合的每日波动；负责失活的肝脏药物代谢酶的昼夜变化；和/或药物排泄率的昼夜变化。
