Pharmacokinetic Analysis of Desmethylmisonidazole (NSC-261,036) and Misonidazole (NSC-261,037) Given Orally or Intravenously to Dogs

摘要

NSC-261,036 and NSC-261,037 were given orally or intravenously (i.v.) to dogs for the purpose of pharmacokinetic analysis. Given i.v., NSC-261,036 has a biexponential plasma elimination behavior that best fits a two-compartment model system. The initial elimination phase (alpha) has its peak plasma concentration not directly related to the admimistered dose. The slope was fairly constant regardless of administered dose with an average value of 0.246 per min. The terminal phase (beta) did have peak plasma concentration values related to administered dose and had a slope of 0.00450 per min. The plasma half-life of the terminal phase (t-one half) was 2.6 hr. The area under the plasma concentration versus time curve (AUC) was dependent upon the administered dose, having average values of 3,722, 2,130 and 1,213 microgram-hr/ml for the 18,000, 9,000, and 4,500 mg/sq m (900, 450 and 225 mg/kg) doses, respectively. The transfer factors, as described by the two-compartment model, were 0.101, 0.0112 and 0.138 per min for k21, k10, and k12, respectively. The volume of distribution for the central compartment (V1) and peripheral compartment (V2) were 326 and 434 ml/kg, respectively.