PMID: 8591721Nov 1, 1995Paper

Pharmacokinetics of YM175, a new bisphosphonate, in rats and dogs

Drug Metabolism and Disposition : the Biological Fate of Chemicals
T UsuiS Higuchi

Abstract

We investigated the pharmacokinetics of YM175, a new bisphosphonate, after intravenous and oral administrations in rats and dogs. After intravenous administration at 0.03-0.3 mg/kg, plasma YM175 concentration declined biexponentially with an apparent terminal half-life of 0.37-0.72 hr in rats and 3.30-4.09 hr in dogs. In both species, the area under the plasma concentration vs. time curve increased dose-proportionally, whereas volume of distribution at steady-state and total body clearance changed little among doses, indicating the linear pharmacokinetics of the drug after intravenous administration. After oral administration to rats (3-30 mg/kg) and dogs (0.3-10 mg/kg), maximum concentration and area under the plasma concentration vs. time curve increased more than dose-proportionally at 30 mg/kg in rats and at 3 mg/kg or higher in dogs. Thus, bioavailability increased at higher doses, being 1.0%, 1.2%, and 3.6% at 3, 10, and 30 mg/kg in rats, and being 1.8%, 1.3%, 2.9%, and 11.5% at 0.3, 1, 3, and 10 mg/kg in dogs, respectively. Urinary excretion and bone concentration of radioactivity in rats receiving [14C]YM175 agreed well with those of unchanged drug in both administration routes, and radiochromatograms of rat urine revea...Continue Reading

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