pharmaceuticals Article Simulation of Physicochemical and Pharmacokinetic Properties of Vitamin D3 and Its Natural Derivatives Subrata Deb * , Anthony Allen Reeves and Suki Lafortune Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, USA;
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[email protected] (S.L.) * Correspondence:
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[email protected]; Tel.: +1-224-310-7870 or +1-305-760-7479 Received: 9 June 2020; Accepted: 20 July 2020; Published: 23 July 2020 Abstract: Vitamin D3 is an endogenous fat-soluble secosteroid, either biosynthesized in human skin or absorbed from diet and health supplements. Multiple hydroxylation reactions in several tissues including liver and small intestine produce different forms of vitamin D3. Low serum vitamin D levels is a global problem which may origin from differential absorption following supplementation. The objective of the present study was to estimate the physicochemical properties, metabolism, transport and pharmacokinetic behavior of vitamin D3 derivatives following oral ingestion. GastroPlus software, which is an in silico mechanistically-constructed simulation tool, was used to simulate the physicochemical and pharmacokinetic behavior for twelve vitamin D3 derivatives. The Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) Predictor and PKPlus modules were employed to derive the relevant parameters from the structural features of the compounds. The majority of the vitamin D3 derivatives are lipophilic (log P values > 5) with poor water solubility which are reflected in the poor predicted bioavailability. The fraction absorbed values for the vitamin D3 derivatives were low except for calcitroic acid, 1,23S,25-trihydroxy-24-oxo-vitamin D3, and (23S,25R)-1,25-dihydroxyvitamin D3-26,23-lactone each being greater than 90% fraction absorbed.