Sandberg J A, Olsen G D
Department of Pharmacology, School of Medicine, Oregon Health Sciences University, Portland.
J Pharmacol Exp Ther. 1991 Aug;258(2):477-82.
The pharmacokinetics of cocaine (COC) were studied during late gestation in guinea pigs. Clearance (Cl) was not dose-dependent and the average +/- S.D. was 59 +/- 16 ml/min/kg over the i.v. dose range of 2 to 12 mg/kg. Volume of distribution at steady state (Vdss), mean resident time (MRT) and elimination half-life (T1/2) were dose-dependent over this dose range with changes occurring between the 2 and the 4 mg/kg dose of COC. Vdss was 2.1 and 3.9 l/kg. MRT time was 42 and 57 min, and elimination T1/2 was 34 and 49 min at the 2 and 4 mg/kg dose, respectively. Cl and Vdss values after 2 to 20 mg/kg of COC s.c. were similar to those after i.v. administration, whereas MRT was significantly greater as a result of delayed absorption. Absorption of COC s.c. was nearly complete (84%) and had a T1/2 of 51 min. Benzoylecgonine (BE) and benzoylnorecgonine (NOR) were major and persistent metabolites of COC. Norcocaine was present after COC doses of 4 mg/kg or higher but could only be detected during the first 2 hr.
在豚鼠妊娠晚期研究了可卡因（COC）的药代动力学。清除率（Cl）不依赖于剂量，静脉注射剂量范围为2至12mg/kg时，平均±标准差为59±16ml/min/kg。在该剂量范围内，稳态分布容积（Vdss）、平均驻留时间（MRT）和消除半衰期（T1/2）均依赖于剂量，在2mg/kg和4mg/kg的COC剂量之间发生变化。Vdss分别为2.1和3.9l/kg。在2mg/kg和4mg/kg剂量下，MRT时间分别为42和57分钟，消除T1/2分别为34和49分钟。皮下注射2至20mg/kg COC后的Cl和Vdss值与静脉注射后的相似，而由于吸收延迟，MRT显著更长。皮下注射COC的吸收几乎完全（84%），T1/2为51分钟。苯甲酰爱康宁（BE）和苯甲酰去甲爱康宁（NOR）是COC的主要且持续存在的代谢产物。在COC剂量为4mg/kg或更高时可检测到去甲可卡因，但仅在最初2小时内可检测到。
