Drug Res (Stuttg) 2017; 67(07): 388-395
DOI: 10.1055/s-0043-101527
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Comparative Pharmacokinetics of Cholecalciferol in Dogs from 2 Different Oral Formulations Using Corrective Measures to Overcome Interference from Endogenous Cholecalciferol

Harilal Patel
1   Bioanalytical/ Drug Metabolism and Pharmacokinetics Laboratory, Ahmedabad, Gujarat, India
,
Prakash Patel
1   Bioanalytical/ Drug Metabolism and Pharmacokinetics Laboratory, Ahmedabad, Gujarat, India
,
Chandrakant Bhatt
1   Bioanalytical/ Drug Metabolism and Pharmacokinetics Laboratory, Ahmedabad, Gujarat, India
,
Ashok Ghoghari
1   Bioanalytical/ Drug Metabolism and Pharmacokinetics Laboratory, Ahmedabad, Gujarat, India
,
Urvesh Patel
1   Bioanalytical/ Drug Metabolism and Pharmacokinetics Laboratory, Ahmedabad, Gujarat, India
,
Mukesh Ukawalal
2   New Drug Delivery System Laboratory, Zydus Research Centre, Ahmedabad, Gujarat, India
,
Shafiq Sheikh
2   New Drug Delivery System Laboratory, Zydus Research Centre, Ahmedabad, Gujarat, India
,
Vikram Ramanathan
1   Bioanalytical/ Drug Metabolism and Pharmacokinetics Laboratory, Ahmedabad, Gujarat, India
,
Nuggehally R. Srinivas
1   Bioanalytical/ Drug Metabolism and Pharmacokinetics Laboratory, Ahmedabad, Gujarat, India
› Author Affiliations
Further Information

Publication History

Publication Date:
26 April 2017 (online)

Abstract

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.

 
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