Belanger P M, Lalande M, Dore F M, Labrecque G
Ecole de pharmacie, Faculté de médecine, Université Laval.
Drug Metab Dispos. 1989 Jan-Feb;17(1):91-7.
The temporal variation in the pharmacokinetics of a single dose administration of isoniazid (INH) and its major metabolite, N-acetylisoniazid (AINH), was investigated at 0900 and 2100 in rats synchronized to a 12-hr light-dark cycle. INH and AINH were administered by the intraarterial and ip routes at a dose of 20 mg/kg, in order to determine the hepatic extraction ratio of both compounds. The mean AUC values of INH obtained after the intraarterial and ip injections of the drug were 42.6 and 8.4 micrograms.hr/ml at 0900 and 30.7 and 12.8 micrograms.hr/ml at 2100, respectively. Consequently, there were temporal variations (mean values at 0900 and 2100) in the clearance (491.6 and 665.3 ml/hr/kg), bioavailability (0.20 and 0.42), hepatic extraction ratio of INH (0.80 and 0.58), and apparent hepatic blood flow (9.7 and 18.6 ml/min). Also, the AUC of AINH was higher at 2100 when INH was injected intraarterially. Likewise, AINH had a lower t 1/2 and AUC values and a higher clearance at 2100, but the hepatic extraction ratio of AINH was 0.26 at 2100 compared with the value of 0.07 at 0900. No diurnal variations were present in the apparent volume of distribution of INH and AINH. In vitro experiments showed that the mean activity of the hepatic N-acetyltransferase was 135.3 nmol/mg at 2100, compared with 59.0 nmol/mg at 0900.(ABSTRACT TRUNCATED AT 250 WORDS)
在与12小时明暗周期同步的大鼠中，于上午9点和晚上9点研究了单剂量给予异烟肼（INH）及其主要代谢产物N - 乙酰异烟肼（AINH）的药代动力学的时间变化。以20mg/kg的剂量通过动脉内和腹腔内途径给予INH和AINH，以确定两种化合物的肝提取率。动脉内和腹腔内注射该药物后获得的INH的平均AUC值在上午9点分别为42.6和8.4微克·小时/毫升，在晚上9点分别为30.7和12.8微克·小时/毫升。因此，清除率（491.6和665.3毫升/小时/千克）、生物利用度（0.20和0.42）、INH的肝提取率（0.80和0.58）以及表观肝血流量（9.7和18.6毫升/分钟）存在时间变化（上午9点和晚上9点的平均值）。此外，当动脉内注射INH时，AINH的AUC在晚上9点更高。同样，AINH在晚上9点具有较低的t1/2和AUC值以及较高的清除率，但AINH的肝提取率在晚上9点为0.26，而上午9点为0.07。INH和AINH的表观分布容积没有昼夜变化。体外实验表明，肝N - 乙酰转移酶的平均活性在晚上9点为135.3纳摩尔/毫克，而上午9点为59.0纳摩尔/毫克。（摘要截断于250字）
