2.9. Pharmacokinetic study in dog

The PH46A capsules were prepared the day before the dosing by weighing a suitable amount of PH46A into each capsule to achieve a target dose level of 100 mg/kg. The capsule fill weights were 1077.4 mg, 1119.6 mg and 990.4 mg for Capsule 1 (001 M), Capsule 2 (002 M) and Capsule 3 (003 M), respectively. Each capsule was administered by placing it in the back of the throat of each animal followed by swallowing and visual confirmation that the capsule was swallowed. Following dosing, blood samples (1 mL) were collected from the jugular vein into tubes containing lithium heparin as an anticoagulant at the following sampling times: pre-dose, 0.25, 0.75, 1, 2, 4, 6, 8, 12 and 24 h post-dose. Plasma was separated by centrifugation (3000 rpm, 10 min & 4 °C) prior to storage at −80 °C until analysis. Individual PH46 plasma concentrations generated were used to estimate pharmacokinetic parameters using WinNonLin v4.1 pharmacokinetic software.