Kinetics of cocaine in humans after intravenous and intranasal administration

Abstract

Cocaine kinetics were studied in four subjects after intravenous and intranasal administration. For intravenous administration cocaine hydrochloride (32 mg) dissolved in physiological saline was injected in 1 ml volume over a 1 min period. Intranasal cocaine was administered as 100 mg powder consisting of an appropriate dose of cocaine hydrochloride (64 and 96 mg) mixed with lactose powder. Subjects were instructed to inhale the mixture through a 5 cm straw within 1 min. Cocaine kinetics, after intravenous injection, conform to a one-compartment open model with first-order elimination. After intranasal administration, cocaine kinetics conform to a one-compartment model with first-order absorption and first-order elimination. The mean half-life of cocaine for intravenous injection in four subjects was 41.4 +/- 8.2 min (mean +/- S.E.M.) and the range was 19 to 64 min. There were statistically significant differences in the mean area under the concentration-time curve (AUC) following intravenous and intranasal administration. The AUC was dose-dependent and the fraction of the dose absorbed after 64 mg intranasal cocaine was significantly lower than after 96 mg dose (p less than 0.05).

The Motivation to Self-Administer is Increased After a History of Spiking Brain Levels of Cocaine

“…A recent survey of experienced cocaine users shows the interval between uses within a cocaine binge might be, on average, well over an hour (Beveridge et al, 2012). Given the short half-life of cocaine (B40 min; Javaid et al, 1983) in humans, these survey data suggest that blood levels are not maintained throughout the binge period but may decrease substantially between each intoxicating event. Although more clinical data on dose size and inter-use interval within a binge would be helpful, it appears that fast-rising and subsequent decline in blood levels is a pattern that can lead individuals down the addiction cycle.…”

“…The inter-use-interval was often much greater than an hour. Given that the half-life of cocaine in humans is B40 min (Javaid et al, 1983), blood concentrations are not maintained at a high level; instead, substantial reductions in blood levels occur which then 'spike' with each intense intoxicating event. It is likely, therefore, that there are qualitative differences in the dynamics of cocaine levels between human drug users and subjects in typical FR cocaine selfadministration experiments.…”

Cocaine Pharmacokinetics in Men and in Women During the Follicular and Luteal Phases of the Menstrual Cycle

“…Since 1977, 11 studies have been conducted with a total of 76 subjects (Barnett et al 1981;Chow et al 1985;Cone 1995;Cone et al 1988;Cook et al 1985;Evans et al 1996;Isenschmid et al 1992;Javaid et al 1978Javaid et al , 1983Jeffcoat et al 1989;Kogan et al 1977). The most recent studies were conducted with six males (Cone 1995) and nine males (Evans et al 1996).…”

“…The most recent studies were conducted with six males (Cone 1995) and nine males (Evans et al 1996). It is not clear if earlier reports in Science (Javaid et al 1978) and Biopharmacology Drug Disposition (Javaid et al 1983) included both men and women. Subjects were described as "adult volunteers," but their gender was not described (Javaid et al 1978(Javaid et al , 1983.…”

“…It is not clear if earlier reports in Science (Javaid et al 1978) and Biopharmacology Drug Disposition (Javaid et al 1983) included both men and women. Subjects were described as "adult volunteers," but their gender was not described (Javaid et al 1978(Javaid et al , 1983. Only one study specifically identified participation by a female subject (Chow et al 1985).…”