Influence of acid or alkaline treatment on tissue distribution and urinary excretion of (3H)-cocaine on acutely treated rats.

The effects of acid (NH4Cl, 60 mg/kg) or alkaline (NaHCO3, 400 mg/kg) pretreatment on tissue disposition and urinary excretion of (3H)-cocaine and its metabolites were assessed in rats. Animals were decapitated 4 hr after 1.9 microCi in 40 mg/kg cocaine (Cl-) in experiments on the biological disposition and the plasma, brain, and liver were assayed. In experiments on urinary excretion, 10 microCi were given and urine was assayed after 18, 24, and 48 hr. Pretreatment with NH4Cl produced a decrease of rates of cocaine + norcocaine in the brain as well as of the polar metabolites (benzoylecgonine, ecgonine benzoylnorecgonine). Forty-eight hours after injection of (3H)-cocaine, NH4Cl produced an increase of the rates of cocaine and its metabolites in the urine. Pretreatment with NaHCO3 causes a decrease of total radioactivity (cocaine + metabolites) in the plasma and in the liver, as well as a decrease of the levels of cocaine + norcocaine in the liver, as well as an increase of the rate of polar metabolites that are excreted in the urine. These data suggest that the decrease of pH after acid treatment produces ionization of basic molecules; these do not penetrate as well in the tissues for which they have no affinity. As a consequence, the urinary excretion is more important. It is possible that alkaline treatment accelerates the excretion of cocaine and its metabolites because it increases diuresis.