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Serum Lipid Levels Following Administration of Solid Dispersion Systems ofProbucol-polyvinylpyrrolidone in Myocardial Infarction-prone Watanabe HeritableHyperlipidemic Rabbits
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JPY
Abstract
Solid dispersion systems of probucol-polyvinylpyrrolidone showed excellent dissolution characteristics and increased bioavailability in normal rabbits. We studied the effect of solid dispersion systems on serum lipid levels to evaluate whether the amount of probucol required might be lesser than that in dosage forms currently available. A solid dispersion system of probucol-polyvinylpyrrolidone(PVP K30)(1:9 weight ratio)were orally administered to myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI)rabbits for 5 weeks. Serum levels of total cholesterol(T-Cho), triglycerides(TG)and phospholipids(PL)are higher in WHHLMI rabbits than in normal rabbits. Following the administration of solid dispersion systems containing 25 mg of probucol, trough plasma concentrations of probucol were significantly higher for up to 5 weeks than those containing 5 mg of probucol. Significant decreases in T-Cho, PL, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were observed following administration of solid dispersion systems containing 25 and 5 mg of probucol. Dose of 5 mg of probucol in rabbits was almost one fifth of the dose of probucol of commercial fine granules in humans by dose per weight.
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