Forrester S D, Brown S A, Lees G E, Hartsfield S M
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station 77843.
Am J Vet Res. 1990 Dec;51(12):2001-5.
Clorazepate dipotassium was administered orally to 8 healthy dogs at a dosage of 2 mg/kg of body weight, q 12 h, for 21 days. Serum disposition of nordiazepam, the principle metabolite of clorazepate, was determined after the first and last dose of clorazepate. Disposition variables were analyzed by use of model-independent pharmacokinetics by the predictive equations method and the trapezoidal rule method. Complete blood counts, serum chemical analyses, and urinalyses were performed before administration of clorazepate and at 10 and 21 days after administration of clorazepate. Maximal nordiazepam concentrations ranged from 446 to 1,542 ng/ml (814 +/- 334 ng/ml), at 59 to 180 minutes (97.9 +/- 42.0 minutes) after a single oral dose of clorazepate. Maximal nordiazepam concentrations ranged from 927 to 1,460 ng/ml (1,308 +/- 187.6 ng/ml), at 120 to 239 minutes (153 +/- 57.9 minutes) after multiple oral doses of clorazepate. Serum disposition was significantly altered after multiple doses of clorazepate. Using data determined by the predictive equations method, the mean residence time after multiple doses (712 +/- 214 minutes) was longer (P less than 0.05) than after a single dose (527 +/- 95.8 minutes). Oral volume of distribution after multiple doses of clorazepate (1.76 +/- 0.647 L/kg) was smaller (P less than 0.02) than after a single dose (3.18 +/- 1.52 L/kg). Oral clearance after multiple doses of clorazepate (3.09 +/- 0.726 ml/min/kg) was less (P less than 0.001) than after a single dose (6.54 +/- 2.15 ml/min/kg). Absorption half-life after multiple doses (72 minutes) was longer (P less than 0.01) than after a single dose (33 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)
以2毫克/千克体重的剂量，每12小时一次，给8只健康犬口服氯氮卓二钾，持续21天。在首次和末次服用氯氮卓后，测定其主要代谢产物去甲西泮的血清处置情况。采用预测方程法和梯形法则法，通过非模型依赖药代动力学分析处置变量。在服用氯氮卓前以及服用后10天和21天进行全血细胞计数、血清化学分析和尿液分析。单次口服氯氮卓后，去甲西泮的最大浓度在446至1542纳克/毫升（814±334纳克/毫升）之间，出现在服药后59至180分钟（97.9±42.0分钟）。多次口服氯氮卓后，去甲西泮的最大浓度在927至1460纳克/毫升（1308±187.6纳克/毫升）之间，出现在服药后120至239分钟（153±57.9分钟）。多次服用氯氮卓后，血清处置情况有显著改变。采用预测方程法确定的数据，多次服药后的平均驻留时间（712±214分钟）比单次服药后（527±95.8分钟）更长（P<0.05）。多次服用氯氮卓后的口服分布容积（1.76±0.647升/千克）比单次服药后（3.18±1.52升/千克）更小（P<0.02）。多次服用氯氮卓后的口服清除率（3.09±0.726毫升/分钟/千克）比单次服药后（6.54±2.15毫升/分钟/千克）更低（P<0.001）。多次服药后的吸收半衰期（72分钟）比单次服药后（33分钟）更长（P<0.01）。（摘要截断于250字）
