Mar 1, 1976

Physiological disposition and biotransformation of (3H) cocaine in acutely and chronically treated rats

The Journal of Pharmacology and Experimental Therapeutics
P K NayakS J Mulé

Abstract

A sensitive method was developed for the estimation of [3H] cocaine in biological materials. After an injection of 8 mg/kg i.v. in male Wistar rats, peak levels in brain, tissues and plasma occurred within 15 minutes and cocaine disappeared completely from brain and plasma 6 hours postinjection. The T1/2 of cocaine in brain and plasma was 0.4 and 0.3 hour, respectively. No significant differences were observed in the rates of disappearance of cocaine from the subcutaneous site in acute and chronically treated rats after an injection of 20 mg/kg. After a 20 mg/kg s. c. dose, the peak levels of cocaine were attained gradually in 4 hours in brain, tissues and plasma with the exception of heart (0.5 hour) and fat (2 hours). These peak levels shifted from 4 to 2 hours in the chronically treated group. Consistently higher levels of cocaine were found to be sequestered in fat in the chronically treated animals. The T1/2 of cocaine in brain and plasma of chronically treated rats was approximately 1.8 to 2 hours and that in the acutely treated animals, 0.8 to 1 hour. The brain/plasma ratios were also somewhat higher in chronically treated as compared to the acutely treated animals and were indicative of a high affinity of tissue for coc...Continue Reading

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Mentioned in this Paper

Subcutaneous Injections
Serum Proteins
Plasma Protein Binding Capacity
Drug-Induced Liver Injury
Absence Epilepsy
Metabolic Biotransformation
Cocaine Hydrochloride
Biliary Sludge

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