The Effect of Lovastatin and Thioridazine on the Degradation of Cocaine in Human Serum In Vitro

Abstract

The effect of lovastatin and thioridazine on the degradation of cocaine in human serum was studied by incubating therapeutic and toxic concentrations of either drug with cocaine in human serum at 37°C. Without these other drugs, cocaine concentrations decreased by an average of 88% in 120 minutes. Lovastatin at all concentrations studied showed a negligible effect on the degradation of cocaine in human serum and did not alter the pseudocholinesterase activity of the serum. In contrast, in the presence of a therapeutic concentration of thioridazine, cocaine concentrations decreased by only 71% during this period of time, and, with a toxic concentration of thioridazine, cocaine concentrations decreased by only 55%. Thioridazine suppressed the pseudocholinesterase activity of human serum by up to 19% during the 120-minute incubation period, and this effect was more pronounced at higher thioridazine concentrations. These findings suggest that thioridazine may prolong the serum half-life of cocaine by inhibiting the pseudocholinesterase-mediated catabolism of cocaine to ecgonine methyl ester. This may be important in cocaine users who are treated with phenothiazines and other structurally similar drugs. They also may be of interest in cocaine-abusing patients who are treated with phenothiazines for schizophrenic disorders.