Drug Interaction of Cimetidine and Cyclosporine in Human

정상지원자에서 Cimetidine과 Cyclosporine의 약물상호작용

The effect of cimetidine administration on the pharmacokinetic parameters of cyclosporine were determined in healthy voluteers. This study was performed in 10 volunteers of age ranged 22-48 years and body weight 48-62 kg. This study was performed with cross-over design. Mono cyclosporine and cyclosporine metabolites was extracted from whole blood analysed by fluororescence polarization immune assay (TDX-FLX, Abbott). After coadministration of cimetidine (300 mg) with cyclosporine (300 mg) orally, maximum concentration of mono cyclosporine was significantly increased $1221{\pm}143\;ng/ml\;to\;1562{\pm}184\;ng/ml$ (P<0.05), area under the time curve of cyclosporine (12 hr) also was significantly increased $7478{\pm}829\;ng/ml{\cdot}hr\;to\;9721{\pm}879\;ng/ml{\cdot}hr$ (P<0.05) and absolute baioavailability of cyclosporine was increased $50\pm5.6\%\;to\;57.6\pm6.1\%\;(P<0.05)$ compared to control group. The blood concentrations of cyclopsorine metabolites were significantly decrased (P<0.05) after coadministration of cimetidine. In cimetidine pretreated group, blood mono cyclosporine concentrations were increased significan시y $1220.0\pm203.00\;ng/ml\;to\;1510.0\pm204.00\;ng/ml$ compared with control group (P<0.05). In the mono cyclosporine pharmacokinetic parameter after oral administration absorption rate and maximum concentration were significantly higher in cimetidine coadministered and pretreated group than control group (P<0.05). The ratio of metabolites and mono cyclosporine concentrations was decreased significantly from $70.8\%\;in\;control\;to\;34.8\%$ in coadministration of cimetidine orally. As matter of facts these reults are considered to inhibition of cyclosporine hepatic metabolism and increasing of cyclosporine absorption rate in gastrointestinal tract because of maintaining cyclosporine stability in elevated gastric pH by cimetidine. We considered, it appeares that cimetidine increase bioavailability of cyclosporine by increasing oral absorption and by decreasing hepatic clearance. But the absorption and clearance of cyclosporine was highly variable individually, and therefore we consider that cyclosporine blood level monitoring would be essential in patients with cimetidine co-administration.