Cocaine pharmacokinetics in the pregnant guinea pig

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.