Pharmacokinetic and pharmacodynamic evaluation of a single dose of new, first in world, high dose aqueous formulation versus conventional oil based preparation of cholecalciferol

Mohit Changani; Ameet Soni; Arani Chatterjee; Ashish Amarsheda; Chandrakant Mavadhiya

doi:10.18203/2320-6012.ijrms20233025

Authors

Mohit Changani Medical Affairs, Cadila Pharmaceuticals Limited, Ahmedabad, Gujarat, India https://orcid.org/0000-0003-0536-0112
Ameet Soni Medical Affairs, Cadila Pharmaceuticals Limited, Ahmedabad, Gujarat, India
Arani Chatterjee CRO, Cadila Pharmaceuticals Limited, Dholka, Gujarat, India
Ashish Amarsheda CRO, Cadila Pharmaceuticals Limited, Dholka, Gujarat, India
Chandrakant Mavadhiya Bioanalytics, Cadila Pharmaceuticals Limited, Dholka, Gujarat, India

DOI:

https://doi.org/10.18203/2320-6012.ijrms20233025

Keywords:

Cholecalciferol, Aqueous formulation, VDD, PKs, PDs

Abstract

Background: Vitamin D deficiency (VDD) is a common condition in India with prevalence in general population varying from 50-94%. VDD has been associated with increased susceptibility to a wide range of viral infections including COVID-19. It is associated with worse outcomes and greater morbidity and mortality in medical as well as surgical ICUs. The objective of the study was to evaluate the pharmacokinetic (PK)/pharmacodynamic (PD) of aqueous cholecalciferol injection in comparison with conventional oil-based injection in VDD healthy adult subjects.

Methods: 24 eligible vitamin D deficient healthy adult males, fulfilling the inclusion/exclusion criteria, were enrolled in the study. Subjects received a single dose of either test (T) [Aqueous cholecalciferol injection 600K IU/2 mL] or reference (R) [Cholecalciferol 600K IU oil-based injection] intramuscularly. Various PK parameters (C_max, AUC0-t, AUC0-∞ and T_max) and PD parameters (concentration of cholecalciferol and 25(OH)D) were measured along with safety analysis.

Results: A significantly higher concentration of cholecalciferol and 25(OH)D were observed with test product compared to reference (p<0.01) from 1-hour post-administration till end of the study. A statistically significant difference between test and reference product was observed for the calculated C_max and T_max for cholecalciferol and 25(OH)D (p<0.0001). All 12 (100%) subject in test arm achieved the normal level of 25(OH)D by 72 hr post-administration as compared to none in reference arm (p=0.0017). There were no serious adverse events (SAEs) or deaths reported during the study.

Conclusions: This first in world, aqueous formulation of cholecalciferol injection was found to be superior in various PK/PD parameters as compared to conventional oil based injection, which resulted in rapid and sustained rise in serum 25(OH)D levels.

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