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- W1969136425 abstract "1. An hplc method with fluorescence derivatization was developed for the quantification of remikiren in plasma (limit of quantification 2 ng/ml). This was used to determine the pharmacokinetics in various species of primate, in which the compound is a potent inhibitor of renin, as well as in the rat and dog in which it is less active. 2. After intravenous administration the mean residence time was < or = 1.5 h in all species, and the plasma clearance approached the corresponding hepatic blood flows. 3. Studies in the bile-duct cannulated rat and dog demonstrated that the high clearance was due to a combination of rapid metabolism, plus biliary and renal excretion of intact drug. 4. Consistent with the high hepatic clearance, oral bioavailability was low ( < or = 6%) in each species. However, all of the species tested absorbed a small proportion of an oral dose extremely rapidly, to give peak concentrations generally within 5 min of administration. 5. 'Simultaneous' collection of blood samples from the hepatic portal vein and aorta of rat confirmed that shortly after oral dosing the intact drug did cross the liver; however, the later collections contained predominantly more polar metabolites. 6. The rapid absorption of intact remikiren is consistent with the transient blockade of plasma renin activity, previously observed in primates after oral administration. However, the high clearance appears inconsistent with the subsequent prolonged decrease in blood pressure, suggesting that the latter effect is mediated through a 'tissue' compartment." @default.
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- W1969136425 date "1996-01-01" @default.
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- W1969136425 title "Pharmacokinetics of remikiren, a potent orally active inhibitor of human renin, in rat, dog and primates" @default.
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- W1969136425 doi "https://doi.org/10.3109/00498259609046712" @default.
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