THE PHARMACOKINETICS OF A POTENTIAL MEMORY-ENHANCING COMPOUND, CL-275838, IN FASTED AND FED VOLUNTEERS

Ten healthy male volunteers received a single oral dose (50mg tablet) of a potential memory-enhancing compound, CL 275 838 administered once after fasting and once with a standard breakfast, in an open, crossover study. Plasma concentrations of unchanged drug, its debenzylated derivative (compound II, the main metabolite) and metabolite IV were measured by liquid chromatography using postcolumn photolysis and fluorometric detection and the calculated pharmacokinetic parameters were compared. Concomitant ingestion of food slightly prolonged the time to peak concentration (by about 1.5 hours), but had no appreciable effect on the maximum plasma concentration, area under the curve, and elimination half-life of CL 275 838. Similar results were obtained with metabolites II and IV. Food did not significantly affect the metabolite-to-parent drug ratios, suggesting that first-pass metabolism and clearance of CL 275 838 are independent of food status. It was concluded that administration of the drug with food of this type would not affect the steady-state concentrations of the parent compound and its active metabolites II and IV. The pharmacological effect of CL 275 838 is therefore unlikely to be altered.