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Aim:To investigate the pharmacokinetic profile and tissue distribution of a novelphosphodiesterase type 5 inhibitor,5-ethyl-2-{5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-2-propoxy-phenyl}-7-propyl-3,5-dihydro-pyrrolo(3,2-d)pyrimidin-4-one(SK-3530),in rats after administration of the ~(14)C-labeled compound.Methods:The pharmacokinetic parameters of SK-3530 were measured based on the totalradioactivity and parent SK-3530 concentration in rat plasma after intravenousand oral administration.The tissue distribution of total radioactivity after a singleoral administration of[~(14)C]SK-3530 at a dose of 40 mg/kg was assayed.Theplasma protein binding rates of SK-3530 were assessed by in vitro and ex vivoassay.Results:The total radioactivity profiles showed linear pharmacokinetics.The maximum plasma concentration and area under the curve of the parent SK3530were 10%-20% compared to those of the total radioactivity.After the oral admin-istration of[~(14)C]SK-3530,the radioactivity was widely distributed in all tissues,and the tissue/plasma ratio of the radioactivity 1 h after administration was calcu-lated as 0.5-2.6 with the exception of excretory organs.A relatively high penetra-tion was shown in the adrenal glands,liver,and lung.In vitro and ex vivo plasmaprotein binding assay by ultrafiltration showed a considerably high binding rateof more than 97%.Conclusion:SK-3530 was relatively well absorbed in the gas-trointestinal tract and showed linear pharmacokinetics over the investigated doserange.SK-3530 had low oral bioavailability due to a high,first-pass metabolism.
Aim: To investigate the pharmacokinetic profile and tissue distribution of a novel phosphodiesterase type 5 inhibitor, 5-ethyl-2- {5- [4- (2-hydroxy- ethyl) -piperazine-1- sulfonyl] -2-propoxy-phenyl} -7-propyl-3,5-dihydro-pyrrolo (3,2-d) pyrimidin-4-one (SK-3530) in rats after administration of the C-labeled compound. Methods: The pharmacokinetic parameters of SK-3530 were measured based on the total radioactivity and parent SK-3530 concentration in rat plasma after intravenousand oral administration. The tissue distribution of total radioactivity after a singleoral administration of [~ (14) C] SK-3530 at a dose of 40 mg / kg was assayed. The total protein activity rates showed linear pharmacokinetics. the maximum plasma concentration and area under the curve of the parent SK 3530were 10% -20 % compared to those of the total radioactivity. After the oral admin-istration of [~ (14) C] SK-3530, the radioactive distributed in all tissues, and the tissue / plasma ratio of the radioactivity 1 h after administration was calcu-lated as 0.5-2.6 with the exception of excretory organs. A relatively high penetration was shown in the adrenal glands, liver, and lung .In vitro and ex vivo plasmaprotein binding assay by ultrafiltration showed a considerably high binding rate of more than 97% .Conclusion: SK-3530 was relatively well absorbed in the gas-trointestinal tract and showed linear pharmacokinetics over the investigated doserange. SK-3530 had low oral bioavailability due to a high, first-pass metabolism.