Pharmacokinetic profile of cocaine following intravenous administration in the female rabbit

Abstract

Prenatal cocaine exposure in a rabbit intravenous model has revealed selective disruption of brain development and pharmacological responsiveness. We therefore examined the pharmacokinetic properties of cocaine in this model. Dutch-belted rabbits were surgically implanted with a catheter in the carotid artery, allowed to recover, and then injected intravenously with a cocaine bolus. Cocaine and benzoylecgonine concentrations were measured in arterial blood plasma and analyzed by nonlinear regression and noncompartmental analyses. Peak cocaine concentration occurred by 30s, was transient, and distribution was rapid. The profile of cocaine in the rabbit is similar to that observed in humans using cocaine at recreational doses.

Prenatal exposure to drugs: effects on brain development and implications for policy and education

“…An intravenous model of prenatal cocaine exposure in the rabbit closely models the pharmacokinetic profile of human abusers 38-40. It has been used to delineate a number of highly specific changes, including altered GABA content in the cortex, altered calcium binding protein expression, morphological changes in pyramidal cells, and decreased dopamine D 1 receptor coupling to its cognate G-protein, G sα 41-46 (Table 1).…”

Pleiotropic Effects of Neurotransmission during Development: Modulators of Modularity

“…This model utilizes a low-dose regimen of intravenous prenatal cocaine exposure in the rabbit, which was initially selected for ease of intravenous administration. Furthermore, the pharmacokinetic profile of intravenous cocaine in the rabbit (Parlaman et al, 2007) closely models what is seen when human users abuse cocaine (Evans et al, 1996; Jenkins et al, 2002), allowing for direct species comparisons and interpretations. A number of studies have established that the prenatal dosing is not teratologic, nor does it impact basic developmental parameters such as kit mortality, litter size, sex or growth rates (L.…”

A new exposure model to evaluate smoked illicit drugs in rodents: A study of crack cocaine

“…Thus, due to the rapid toxicokinetics of the smoked form of cocaine (Jatlow, 1988), the animals exposed to 100 mg for 10 min in addition to the 5 min wait for euthanasia would exhibit plasma concentrations below than animals that were only exposed to 100 mg for 5 min. Indeed, studies in humans (Evans et al, 1996) and animals (He et al, 2006;Parlaman et al, 2007) demonstrated that the peak concentration and bioavailability of the administration of intravenous and smoked cocaine occurred 5-15 s after exposure with a very significant decrease in concentration 5 min after administration.…”

“…The PF group was used to determine whether any observed abnormal behaviors was due to the direct effect of the crack or resulted from reduced food intake or dietary deficiencies. Studies performed with injected cocaine and crack cocaine in humans (Evans, Cone, & Henningfield, 1996) and animals (He et al, 2006;Parlaman, Thompson, Levitt, & Stanwood, 2007) demonstrated that peak cocaine concentrations and bioavailability occur within 5-15 s after exposure, with a significant decrease in levels 5 min after exposure. The exposure chamber used in this study could only accommodate a maximum of 5 animals at a time.…”