Pharmacokinetic study of (S)-(−)-2-(N-propyl-N-(2-thienylethyl)amino)-5-hydroxytetralin infusion in cynomolgus monkeys

✍ Scribed by Denise R. Lowe Walters; William R. McConnell; Eugenio A. Cefali

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 295 KB
• Volume: 83
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600830533

✦ Synopsis

A pharmacokinetic study of the dopamine 0 2 receptor agonist ( S)-(-)-2-(Npropyl-N(2-thienylethyl)amino)-5-hydroxytetralimHCl (K0923) infused in female cynomolgus monkeys over a 4-h period was carried out at International Research and Development Corporation. The purpose of this study was to estimate the elimination half-life and elucidate the dose-clearance relationship in cynomolgus monkeys with a randomized three-way crossover intravenous (iv) infusion study design. Six female cynomolgus monkeys were dosed by iv infusion for 4 h with 0.1,0.5, and 1.0 mg/kg/h. Plasma samples were drawn during the infusion and up to 4 h post infusion. The plasma concentrations were determined by a sensitive and specific HPLC assay with electrochemical detection after solid-phase extraction at the Department of Toxicology and Bioanalysis at the University Center for Pharmacy in Gronigen, The Netherlands. The plasma data were best described by a two-compartment open model. Mean elimination half-lives of 36.8, 39.6, and 52.4 min and mean clearance values of 229 f 35,202 f 85, and 191 f 36 mL/min/kg were obtained for doses of 0.1, 0.5, and 1.0 mg/kg/h, respectively. The steadystate volumes of distribution were estimated as 3.89 f 0.816, 3.53 f 1.62, and 4.70 f 3.67 Llkg for the same doses, respectively. There were no significant differences between any of the estimated pharmacokinetic parameters for any of the infusion doses. Clearance was not dose dependent and steady-state plasma concentration appeared directly proportional to dose, suggesting linear pharmacokinetics in this dose range for monkeys.