Simulation of Physicochemical and Pharmacokinetic Properties of Vitamin D<sub>3</sub> and Its Natural Derivatives
Vitamin D<sub>3</sub> 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 D<sub>3</s...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-07-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/13/8/160 |
| _version_ | 1797561615138160640 |
|---|---|
| author | Subrata Deb Anthony Allen Reeves Suki Lafortune |
| author_facet | Subrata Deb Anthony Allen Reeves Suki Lafortune |
| author_sort | Subrata Deb |
| collection | DOAJ |
| description | Vitamin D<sub>3</sub> 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 D<sub>3</sub>. 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 D<sub>3</sub> 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 D<sub>3</sub> 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 D<sub>3</sub> derivatives are lipophilic (log <i>P</i> values >5) with poor water solubility which are reflected in the poor predicted bioavailability. The fraction absorbed values for the vitamin D<sub>3</sub> derivatives were low except for calcitroic acid, 1,23<i>S</i>,25-trihydroxy-24-oxo-vitamin D<sub>3</sub>, and (23<i>S</i>,25<i>R</i>)-1,25-dihydroxyvitamin D<sub>3</sub>-26,23-lactone each being greater than 90% fraction absorbed. Cytochrome P450 3A4 (CYP3A4) is the primary hepatic enzyme along with P-glycoprotein involved in the disposition of the vitamin D derivatives. Lipophilicity and solubility appear to be strongly associated with the oral absorption of the vitamin D<sub>3</sub> derivatives. Understanding the ADME properties of vitamin D<sub>3</sub> derivatives with the knowledge of pharmacological potency could influence the identification of pharmacokinetically most acceptable vitamin D<sub>3</sub> derivative for routine supplementation. |
| first_indexed | 2024-03-10T18:16:27Z |
| format | Article |
| id | doaj.art-ea92409a29ed4bc2aba73785ae65c62b |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T18:16:27Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-ea92409a29ed4bc2aba73785ae65c62b2023-11-20T07:41:39ZengMDPI AGPharmaceuticals1424-82472020-07-0113816010.3390/ph13080160Simulation of Physicochemical and Pharmacokinetic Properties of Vitamin D<sub>3</sub> and Its Natural DerivativesSubrata Deb0Anthony Allen Reeves1Suki Lafortune2Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, USAVitamin D<sub>3</sub> 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 D<sub>3</sub>. 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 D<sub>3</sub> 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 D<sub>3</sub> 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 D<sub>3</sub> derivatives are lipophilic (log <i>P</i> values >5) with poor water solubility which are reflected in the poor predicted bioavailability. The fraction absorbed values for the vitamin D<sub>3</sub> derivatives were low except for calcitroic acid, 1,23<i>S</i>,25-trihydroxy-24-oxo-vitamin D<sub>3</sub>, and (23<i>S</i>,25<i>R</i>)-1,25-dihydroxyvitamin D<sub>3</sub>-26,23-lactone each being greater than 90% fraction absorbed. Cytochrome P450 3A4 (CYP3A4) is the primary hepatic enzyme along with P-glycoprotein involved in the disposition of the vitamin D derivatives. Lipophilicity and solubility appear to be strongly associated with the oral absorption of the vitamin D<sub>3</sub> derivatives. Understanding the ADME properties of vitamin D<sub>3</sub> derivatives with the knowledge of pharmacological potency could influence the identification of pharmacokinetically most acceptable vitamin D<sub>3</sub> derivative for routine supplementation.https://www.mdpi.com/1424-8247/13/8/160vitamin D<sub>3</sub>cytochrome P450lipophilicitysolubilitypharmacokineticsphysicochemical |
| spellingShingle | Subrata Deb Anthony Allen Reeves Suki Lafortune Simulation of Physicochemical and Pharmacokinetic Properties of Vitamin D<sub>3</sub> and Its Natural Derivatives Pharmaceuticals vitamin D<sub>3</sub> cytochrome P450 lipophilicity solubility pharmacokinetics physicochemical |
| title | Simulation of Physicochemical and Pharmacokinetic Properties of Vitamin D<sub>3</sub> and Its Natural Derivatives |
| title_full | Simulation of Physicochemical and Pharmacokinetic Properties of Vitamin D<sub>3</sub> and Its Natural Derivatives |
| title_fullStr | Simulation of Physicochemical and Pharmacokinetic Properties of Vitamin D<sub>3</sub> and Its Natural Derivatives |
| title_full_unstemmed | Simulation of Physicochemical and Pharmacokinetic Properties of Vitamin D<sub>3</sub> and Its Natural Derivatives |
| title_short | Simulation of Physicochemical and Pharmacokinetic Properties of Vitamin D<sub>3</sub> and Its Natural Derivatives |
| title_sort | simulation of physicochemical and pharmacokinetic properties of vitamin d sub 3 sub and its natural derivatives |
| topic | vitamin D<sub>3</sub> cytochrome P450 lipophilicity solubility pharmacokinetics physicochemical |
| url | https://www.mdpi.com/1424-8247/13/8/160 |
| work_keys_str_mv | AT subratadeb simulationofphysicochemicalandpharmacokineticpropertiesofvitamindsub3subanditsnaturalderivatives AT anthonyallenreeves simulationofphysicochemicalandpharmacokineticpropertiesofvitamindsub3subanditsnaturalderivatives AT sukilafortune simulationofphysicochemicalandpharmacokineticpropertiesofvitamindsub3subanditsnaturalderivatives |