Single oral dose of pravastatin exceeded target plasma concentrations and displayed a favorable pharmacokinetic profile in cockatiels (Nymphicus hollandicus)

Abstract

Objective To evaluate the plasma concentrations and determine the pharmacokinetic profile of pravastatin after administratioof a single oral dose in cockatiels. Methods A pilot study was performed at single oral doses of 20, 40, and 80 mg/kg. Based on the results of the pilot study, 14 adult cockatiels (7 male and 7 female) were administered a 40-mg/kg dose using a compounded oral suspen-sion of pravastatin via oral gavage. Blood samples were collected at 7 different time points from 0.5 to 12 hours after administration in a balanced incomplete block design, with 3 blood samples/bird and 6 replicates/time point. Plasma concentrations of pravastatin were determined via LC-MS-MS. Pharmacokinetic analysis was performed using compartmental analysis. Results The estimated time to maximum concentration, maximum plasma concentration, and terminal half-life were 2 hours, 669.9 ng/mL, and 3 hours, respectively. There was high interindividual variability, and 1 cockatiel had extremely high levels of pravastatin through all sample points and was excluded from the analysis. Conclusions A single oral dose of 40 mg/kg of pravastatin administered to cockatiels exceeded plasma concentrations that would be considered therapeutic in humans (45 to 55 ng/mL). Clinical Relevance A starting dose of 40 mg/kg, PO, every 24 hours or lower has the potential of being beneficial in the treatment ocockatiels with lipid disorders pending further investigations with multidose pharmacokinetic studies, efficacy studies evaluating hypolipidemic effect, and its possible administration in drinking water.