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• W1889385502 abstract "Clevidipine is a new vascular selective calcium channel antagonist of the dihydropyridine type, structurally related to felodipine. Clinical trials have shown that the drug can be used to effectively control the blood pressure in connection with cardiac surgical procedures. The compound is tailored to be a short-acting drug and, due to incorporation of an ester linkage into the drug molecule, clevidipine is rapidly metabolized by ester hydrolysis. The pharmacokinetics of clevidipine and its primary metabolite, H 152/81, were studied in rats, rabbits, and dogs. In addition, the influence of the pharmacokinetics on the effect on mean arterial blood pressure was evaluated in anesthetized dogs. Compartmental nonlinear mixed effect regression analysis was used to calculate the population mean and individual pharmacokinetics of clevidipine, whereas nonlinear regression analysis of individual data was used to determine the pharmacokinetics of the primary metabolite. A linked Emax model was fitted to the individual pharmacodynamic/pharmacokinetic data in dogs. According to the results, clevidipine is a high-clearance drug with a relatively small volume of distribution, resulting in an extremely short half-life in all species studied. The median initial half-life of the individual value (Bayesian estimates) is 12, 20, and 22 s in the rabbit, rat, and dog, respectively. The primary metabolite is a high-clearance compound in the dog, whereas it is a low-clearance compound in the rat. A significant gender difference in the clearance of the metabolite was observed in the rat. The mean maximum reduction in arterial blood pressure is 38 +/- 12% (Emax) and is achieved at 85 +/- 46 nM (EC50). The half-life for reaching equilibrium between the central and the effect compartment (T1/2ke0) is 47 +/- 49 s." @default.
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• W1889385502 date "1999-05-01" @default.
• W1889385502 modified "2023-09-23" @default.
• W1889385502 title "Pharmacokinetics of new calcium channel antagonist clevidipine in the rat, rabbit, and dog and pharmacokinetic/pharmacodynamic relationship in anesthetized dogs." @default.
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