Sildenafil Plasma Concentration: Time Profile After Cimetidine Co-Administration

Abstract

To assess the plasma concentration-time profile of sildenafil alone and after a single dose (400 mg) of cimetidine, with other pharmacokinetic parameters, a study was conducted at the Department of Pharmaco- logy, College of Medicine and Department of Che-mistry, College of Science, University of Mosul, from May 2008-June 2008. Twelve healthy volunteers were each given a sildenafil tablet 50 mg and blood samples were drawn at 0, 0.5,1, 2, 4, 6, 8,10 and 12 hours after administration. After a one week washout period, the same volunteers were given cimetidine 400 mg followed two hours later by sildenafil 50 mg and blood samples drawn at 0, 0.5,1,2, 4, 6, 8,10 and 12 hours after the sildenafil administration. Using high performance liquid chromatography (HPLC) for analysis, the concentration-time profile, half-life (t1 /2), area under the curve (AUC), k (elimination) were measured. Maximum plasma concentration (Cmax) and time to reach maximum plasma concentration (T max) were calculated. Co-administration of cimetidine resulted in significantly higher plasma concentrations of sildenafil, reflected by a significant rise in AUC (p < 0.0001) and a significant increase in C max (p < 0.0001). The k (elimination) of sildenafil was significantly delayed (p < 0.0001) and the elimination half-life was prolonged (p < 0.0001). Cimetidine through its action as an inhibitor of Cytochrome P3 A4 (the metabolic pathway of sildenafil) increases the plasma level of sildenafil as reflected by the increase in AUC, C max, 11 /2 and a significant reduction in k(elimination).