Cocaine inhalation in the rat: pharmacokinetics and cardiovascular response.
Despite the great attention given to the pharmacological actions of cocaine in recent years, the mechanisms leading to acute intoxication and related deaths after cocaine smoking have not been fully elucidated. The present study was therefore undertaken to examine the pharmacokinetics and pharmacological effects of cocaine by the inhalation route. Cannulated, male Sprague-Dawley rats were exposed to a constant concentration of cocaine vapor (13.6 +/- 0.4 micrograms cocaine per ml mainstream air), during which time their biodispositional profile and cardiovascular responses were evaluated. The bioavailable doses of cocaine were 0.26 +/- 0.05 and 1.54 +/- 0.46 mg/kg, after 1.5- and 5.0-min exposures, respectively. Peak cocaine plasma concentrations of 95 +/- 26 and 205 +/- 58 ng/ml, for the 1.5- and 5.0-min exposures, respectively, occurred 1 min after the start of exposure. Increasing the duration of exposure significantly increased the bioavailability from 0.29 to 1.03 (P less than .05). Transient changes in heart rate and arterial blood pressure were generally dose-dependent and correlated temporally with peak cocaine plasma concentrations. During exposure, 70% of the animals demonstrated electrophysiological aberrations consistent with atrial arrhythmia and incomplete heart block. These findings suggest that a direct cardiotoxic effect resulted from inhalation of cocaine.
Boni
J P
JP
Department of Pharmacology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Barr
W H
WH
Martin
B R
BR
D000042:Absorption; D000280:Administration, Inhalation; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D008168:Lung / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D014835:Volatilization
C005618:benzoylecgonine; D003042:Cocaine