Cocaine pharmacokinetics in humans

Area of Science:

• Pharmacology and Toxicology
• Drug Metabolism and Pharmacokinetics

Background:

• Cocaine is a stimulant drug with significant abuse potential.
• Understanding cocaine pharmacokinetics is crucial for clinical and forensic toxicology.

Purpose of the Study:

• To investigate the dose-dependent pharmacokinetic parameters of cocaine in humans.
• To compare absorption and bioavailability across different routes of administration.

Main Methods:

• Cocaine administered intravenously to human subjects.
• Plasma concentrations measured using gas chromatography-mass spectrometry.
• Analysis of previously published data for absorption characteristics.

Main Results:

• Significant dose-dependent relationships observed for key pharmacokinetic parameters.
• Terminal plasma half-life (t1/2(beta)) increases with dose: t1/2(beta) = 13.5 + 24.5 * dose.
• Total plasma clearance decreases with dose: Clearance = 2.51 - 0.67 * dose.
• Absorption half-life (t1/2(ab)) approximately 8 minutes for gastrointestinal and nasal routes.
• Nasal inhalation bioavailability estimated at 60%.

Conclusions:

• Cocaine pharmacokinetics are highly dose-dependent in humans.
• Recreational routes like nasal inhalation may lead to drug accumulation.
• Chewing coca leaves is unlikely to cause significant blood accumulation.