Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Walters, D.R. et al.

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

A pharmacokinetic study of the dopamine D2 receptor agonist (S)-(-)-2-(N-propyl-N-(2-thienylethyl)amino)-5-hydroxytetralin+ ++-HCl (N-0923) 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 Groningen, 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 +/- 35, 202 +/- 85, and 191 +/- 36 mL/min/kg were obtained for doses of 0.1, 0.5, and 1.0 mg/kg/h, respectively. The steady-state volumes of distribution were estimated as 3.89 +/- 0.816, 3.53 +/- 1.62, and 4.70 +/- 3.67 L/kg 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.[1]

References

Pharmacokinetic study of (S)-(-)-2-(N-propyl-N-(2-thienylethyl)amino)-5-hydroxytetralin infusion in cynomolgus monkeys. Walters, D.R., McConnell, W.R., Cefali, E.A. Journal of pharmaceutical sciences. (1994) [Pubmed]

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