Therapeutic targets of vitamin D receptor ligands and their pharmacokinetic effects by modulation of transporters and metabolic enzymes

Vitamin D is involved in retaining the balance of several minerals in the body, such as calcium and phosphate, which are crucial for the bone formation and development. These physiological effects of vitamin D are mediated by activation of the transcription factor vitamin D receptor (VDR). Moreover,...

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Published inJournal of pharmaceutical investigation Vol. 50; no. 1; pp. 1 - 16
Main Authors Choi, Min Sik, Kim, Yu Chul, Maeng, Han-Joo
Format Journal Article
LanguageEnglish
Published Singapore Springer Singapore 01.01.2020
한국약제학회
Subjects
Biomedical and Life Sciences
Biomedicine
Review
약학
Vitamin D receptor (VDR)
Transporters
Vitamin D
Pharmacokinetics
Metabolic enzymes
Therapeutic target
Online AccessGet full text
ISSN2093-5552
2093-6214
DOI10.1007/s40005-019-00429-z

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Abstract Vitamin D is involved in retaining the balance of several minerals in the body, such as calcium and phosphate, which are crucial for the bone formation and development. These physiological effects of vitamin D are mediated by activation of the transcription factor vitamin D receptor (VDR). Moreover, vitamin D is closely related to several pathological conditions including osteoporosis, secondary hyperparathyroidism, cancer, psoriasis and autoimmune diseases, which is not only due to calcemic but also non-calcemic effects of vitamin D such as cell proliferation, differentiation, and immunomodulation. These various abilities of vitamin D have made VDR an attractive therapeutic target. Already, numerous vitamin D analogs have been developed and studied in in vitro disease models or animal models, and some have been in clinical trials or approved for the treatment of certain diseases. In addition, the transcriptional and/or post-transcriptional regulation by VDR activation also affects the genes involved in drug metabolism and disposition, possibly leading to pharmacokinetic changes of several drugs in clinical use. This review provides a detailed summary of therapeutic targets of VDR ligands, and their effects on the transporters and metabolic enzymes, causing in vitro and in vivo pharmacokinetic changes of several drugs. The clinical research is further required for the confirming the clinical relevance of pharmacokinetic drug interactions by VDR ligands.
AbstractList Vitamin D is involved in retaining the balance of several minerals in the body, such as calcium and phosphate, which are crucial for the bone formation and development. These physiological effects of vitamin D are mediated by activation of the transcription factor vitamin D receptor (VDR). Moreover, vitamin D is closely related to several pathological conditions including osteoporosis, secondary hyperparathyroidism, cancer, psoriasis and autoimmune diseases, which is not only due to calcemic but also non-calcemic effects of vitamin D such as cell proliferation, differentiation, and immunomodulation. These various abilities of vitamin D have made VDR an attractive therapeutic target. Already, numerous vitamin D analogs have been developed and studied in in vitro disease models or animal models, and some have been in clinical trials or approved for the treatment of certain diseases. In addition, the transcriptional and/or post-transcriptional regulation by VDR activation also affects the genes involved in drug metabolism and disposition, possibly leading to pharmacokinetic changes of several drugs in clinical use. This review provides a detailed summary of therapeutic targets of VDR ligands, and their effects on the transporters and metabolic enzymes, causing in vitro and in vivo pharmacokinetic changes of several drugs. The clinical research is further required for the confirming the clinical relevance of pharmacokinetic drug interactions by VDR ligands. KCI Citation Count: 7
Vitamin D is involved in retaining the balance of several minerals in the body, such as calcium and phosphate, which are crucial for the bone formation and development. These physiological effects of vitamin D are mediated by activation of the transcription factor vitamin D receptor (VDR). Moreover, vitamin D is closely related to several pathological conditions including osteoporosis, secondary hyperparathyroidism, cancer, psoriasis and autoimmune diseases, which is not only due to calcemic but also non-calcemic effects of vitamin D such as cell proliferation, differentiation, and immunomodulation. These various abilities of vitamin D have made VDR an attractive therapeutic target. Already, numerous vitamin D analogs have been developed and studied in in vitro disease models or animal models, and some have been in clinical trials or approved for the treatment of certain diseases. In addition, the transcriptional and/or post-transcriptional regulation by VDR activation also affects the genes involved in drug metabolism and disposition, possibly leading to pharmacokinetic changes of several drugs in clinical use. This review provides a detailed summary of therapeutic targets of VDR ligands, and their effects on the transporters and metabolic enzymes, causing in vitro and in vivo pharmacokinetic changes of several drugs. The clinical research is further required for the confirming the clinical relevance of pharmacokinetic drug interactions by VDR ligands.
Author Maeng, Han-Joo
Choi, Min Sik
Kim, Yu Chul
Author_xml – sequence: 1
  givenname: Min Sik
  surname: Choi
  fullname: Choi, Min Sik
  organization: Lab of Pharmacology, College of Pharmacy, Dongduk Women’s University
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  givenname: Yu Chul
  surname: Kim
  fullname: Kim, Yu Chul
  email: yckim@inje.ac.kr
  organization: Department of Pharmaceutical Engineering, Inje University
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  givenname: Han-Joo
  surname: Maeng
  fullname: Maeng, Han-Joo
  email: hjmaeng@gachon.ac.kr
  organization: College of Pharmacy, Gachon University
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Keywords Vitamin D receptor (VDR)
Transporters
Vitamin D
Pharmacokinetics
Metabolic enzymes
Therapeutic target
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Snippet Vitamin D is involved in retaining the balance of several minerals in the body, such as calcium and phosphate, which are crucial for the bone formation and...
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Title Therapeutic targets of vitamin D receptor ligands and their pharmacokinetic effects by modulation of transporters and metabolic enzymes
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