RESUMEN
The aim of the preclinical investigation was to obtain single dose pharmacokinetics in dogs from 2 different oral cholecalciferol formulations using corrective measures to overcome the interference of endogenous cholecalciferol. 6 dogs were fasted overnight and the following day received 60 000 IU dose cholecalciferol [reference, Eris®, vs. test, Sunbless®] by oral dosing. Blood samples were collected on day 0 (baseline establishment) and after dosing on day 1 up to 28 days. The serum samples were extracted using protein precipitation/solid phase extraction and analysed to determine cholecalciferol by LC-MS/MS assay with calibrators prepared from cholecalciferol free serum. Standard pharmacokinetic analysis was carried out to assess pharmacokinetic parameters. An un-paired t-test was employed for comparing statistical significance between formulations. Serum cholecalciferol concentration vs. time profiles for the 2 formulations was almost superimposable. None of the pharmacokinetic parameters showed statistically significant differences (p>0.05) between the 2 treatments. For example: Cmax (ng/mL) and AUCinf (ng.h/mL) derived after the baseline corrections were 708.65 and 38 877.18 for reference and 743.71 and 40 665.51 for test, respectively. Pharmacokinetics of cholecalciferol was comparable between reference vs. test formulations. The procedures, baseline correction and employment of cholecalciferol devoid serum, can be readily adopted in future pharmacokinetic studies in animals or humans.
