Role of vitamin D pathway gene polymorphisms on rifampicin plasma and intracellular pharmacokinetics

We retrospectively evaluate the pharmacogenetic role of single nucleotide polymorphisms involved in rifampicin transport ( , and genes) and vitamin D ( , and genes) metabolism and activity on drug plasma and intracellular concentrations. Rifampicin C and C were measured at weeks 2 and 4 using Ultra-...

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Published inPharmacogenomics Vol. 19; no. 9; pp. 865 - 880
Main Authors Allegra, Sarah, Fatiguso, Giovanna, Calcagno, Andrea, Baietto, Lorena, Motta, Ilaria, Favata, Fabio, Cusato, Jessica, Bonora, Stefano, Di Perri, Giovanni, D'Avolio, Antonio
Format Journal Article
LanguageEnglish
Published England Future Medicine Ltd 01.06.2017
Subjects
Adult
Alleles
Antimicrobial agents
Drug dosages
Drug metabolism
Female
Gene expression
Genomics
Genotype
Glycoproteins
Humans
Influence
Intracellular
Leukocytes (mononuclear)
Liquid chromatography
Male
Mass spectroscopy
MDR1 protein
Middle Aged
Mutation
Pharmacokinetics
Plasma - metabolism
Polymerase chain reaction
Polymorphism
Polymorphism, Single Nucleotide - genetics
Retrospective Studies
Rifampin
Rifampin - blood
Rifampin - pharmacokinetics
RNA polymerase
Single-nucleotide polymorphism
Solute Carrier Organic Anion Transporter Family Member 1b1 - genetics
Tuberculosis
Vitamin D
Vitamin D - genetics
Vitamin D receptors
Vitamin deficiency
TaqI
ABCB1
CYP24A1
Cdx2
FokI
tuberculosis
pharmacokinetics
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Abstract We retrospectively evaluate the pharmacogenetic role of single nucleotide polymorphisms involved in rifampicin transport ( , and genes) and vitamin D ( , and genes) metabolism and activity on drug plasma and intracellular concentrations. Rifampicin C and C were measured at weeks 2 and 4 using Ultra-Performance Liquid Chromatography-tandem mass spectroscopy methods. Allelic discrimination was performed by real-time polymerase chain reaction. Twenty-four patients were enrolled. At week 2, TT and + CC/CT considering plasma and AA for intraperipheral blood mononuclear cells C , remained in regression analysis. Concerning week 4, ITC/CC and CT/TT were retained in plasma C regression model. This study confirms the role of SLCO1B1 and it suggests the involvement of vitamin D pathway gene polymorphisms in rifampicin pharmacokinetics.
AbstractList Aim: We retrospectively evaluate the pharmacogenetic role of single nucleotide polymorphisms involved in rifampicin transport (SLCO1B1, MDR1 and PXR genes) and vitamin D (VDR, CYP24A1 and CYP27B1 genes) metabolism and activity on drug plasma and intracellular concentrations. Patients & methods: Rifampicin Cmax and Ctrough were measured at weeks 2 and 4 using Ultra-Performance Liquid Chromatography–tandem mass spectroscopy methods. Allelic discrimination was performed by real-time polymerase chain reaction. Results: Twenty-four patients were enrolled. At week 2, OATP1B1 521TT and CYP27B1 +2838CC/CT considering plasma and BsmIAA for intraperipheral blood mononuclear cells Cmax, remained in regression analysis. Concerning week 4, TaqITC/CC and CYP24A1 22776CT/TT were retained in plasma Cmax regression model. Conclusion: This study confirms the role of SLCO1B1 and it suggests the involvement of vitamin D pathway gene polymorphisms in rifampicin pharmacokinetics.
We retrospectively evaluate the pharmacogenetic role of single nucleotide polymorphisms involved in rifampicin transport ( , and genes) and vitamin D ( , and genes) metabolism and activity on drug plasma and intracellular concentrations. Rifampicin C and C were measured at weeks 2 and 4 using Ultra-Performance Liquid Chromatography-tandem mass spectroscopy methods. Allelic discrimination was performed by real-time polymerase chain reaction. Twenty-four patients were enrolled. At week 2, TT and + CC/CT considering plasma and AA for intraperipheral blood mononuclear cells C , remained in regression analysis. Concerning week 4, ITC/CC and CT/TT were retained in plasma C regression model. This study confirms the role of SLCO1B1 and it suggests the involvement of vitamin D pathway gene polymorphisms in rifampicin pharmacokinetics.
We retrospectively evaluate the pharmacogenetic role of single nucleotide polymorphisms involved in rifampicin transport (SLCO1B1, MDR1 and PXR genes) and vitamin D (VDR, CYP24A1 and CYP27B1 genes) metabolism and activity on drug plasma and intracellular concentrations.AIMWe retrospectively evaluate the pharmacogenetic role of single nucleotide polymorphisms involved in rifampicin transport (SLCO1B1, MDR1 and PXR genes) and vitamin D (VDR, CYP24A1 and CYP27B1 genes) metabolism and activity on drug plasma and intracellular concentrations.Rifampicin Cmax and Ctrough were measured at weeks 2 and 4 using Ultra-Performance Liquid Chromatography-tandem mass spectroscopy methods. Allelic discrimination was performed by real-time polymerase chain reaction.PATIENTS & METHODSRifampicin Cmax and Ctrough were measured at weeks 2 and 4 using Ultra-Performance Liquid Chromatography-tandem mass spectroscopy methods. Allelic discrimination was performed by real-time polymerase chain reaction.Twenty-four patients were enrolled. At week 2, OATP1B1 521TT and CYP27B1 +2838CC/CT considering plasma and BsmIAA for intraperipheral blood mononuclear cells Cmax, remained in regression analysis. Concerning week 4, TaqITC/CC and CYP24A1 22776CT/TT were retained in plasma Cmax regression model.RESULTSTwenty-four patients were enrolled. At week 2, OATP1B1 521TT and CYP27B1 +2838CC/CT considering plasma and BsmIAA for intraperipheral blood mononuclear cells Cmax, remained in regression analysis. Concerning week 4, TaqITC/CC and CYP24A1 22776CT/TT were retained in plasma Cmax regression model.This study confirms the role of SLCO1B1 and it suggests the involvement of vitamin D pathway gene polymorphisms in rifampicin pharmacokinetics.CONCLUSIONThis study confirms the role of SLCO1B1 and it suggests the involvement of vitamin D pathway gene polymorphisms in rifampicin pharmacokinetics.
We retrospectively evaluate the pharmacogenetic role of single nucleotide polymorphisms involved in rifampicin transport (SLCO1B1, MDR1 and PXR genes) and vitamin D (VDR, CYP24A1 and CYP27B1 genes) metabolism and activity on drug plasma and intracellular concentrations. Rifampicin C and C were measured at weeks 2 and 4 using Ultra-Performance Liquid Chromatography-tandem mass spectroscopy methods. Allelic discrimination was performed by real-time polymerase chain reaction. Twenty-four patients were enrolled. At week 2, OATP1B1 521TT and CYP27B1 +2838CC/CT considering plasma and BsmIAA for intraperipheral blood mononuclear cells C , remained in regression analysis. Concerning week 4, TaqITC/CC and CYP24A1 22776CT/TT were retained in plasma C regression model. This study confirms the role of SLCO1B1 and it suggests the involvement of vitamin D pathway gene polymorphisms in rifampicin pharmacokinetics.
Author Baietto, Lorena
Allegra, Sarah
D'Avolio, Antonio
Fatiguso, Giovanna
Cusato, Jessica
Bonora, Stefano
Calcagno, Andrea
Motta, Ilaria
Favata, Fabio
Di Perri, Giovanni
AuthorAffiliation 1Laboratory of Clinical Pharmacology & Pharmacogenetics, Department of Medical Sciences, Unit of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, Corso Svizzera 164, 10149 Turin, Italy
AuthorAffiliation_xml – name: 1Laboratory of Clinical Pharmacology & Pharmacogenetics, Department of Medical Sciences, Unit of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, Corso Svizzera 164, 10149 Turin, Italy
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Snippet We retrospectively evaluate the pharmacogenetic role of single nucleotide polymorphisms involved in rifampicin transport ( , and genes) and vitamin D ( , and...
We retrospectively evaluate the pharmacogenetic role of single nucleotide polymorphisms involved in rifampicin transport (SLCO1B1, MDR1 and PXR genes) and...
Aim: We retrospectively evaluate the pharmacogenetic role of single nucleotide polymorphisms involved in rifampicin transport (SLCO1B1, MDR1 and PXR genes) and...
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futurescience
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StartPage 865
SubjectTerms Adult
Alleles
Antimicrobial agents
Drug dosages
Drug metabolism
Female
Gene expression
Genomics
Genotype
Glycoproteins
Humans
Influence
Intracellular
Leukocytes (mononuclear)
Liquid chromatography
Male
Mass spectroscopy
MDR1 protein
Middle Aged
Mutation
Pharmacokinetics
Plasma - metabolism
Polymerase chain reaction
Polymorphism
Polymorphism, Single Nucleotide - genetics
Retrospective Studies
Rifampin
Rifampin - blood
Rifampin - pharmacokinetics
RNA polymerase
Single-nucleotide polymorphism
Solute Carrier Organic Anion Transporter Family Member 1b1 - genetics
Tuberculosis
Vitamin D
Vitamin D - genetics
Vitamin D receptors
Vitamin deficiency
Title Role of vitamin D pathway gene polymorphisms on rifampicin plasma and intracellular pharmacokinetics
URI http://dx.doi.org/10.2217/pgs-2017-0176
https://www.ncbi.nlm.nih.gov/pubmed/28594304
https://www.proquest.com/docview/2326938980
https://www.proquest.com/docview/1907322782
Volume 19
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