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

• Published in: Pharmacogenomics 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
• Language: English
• 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
• ISSN: 1462-2416; 1744-8042; 1744-8042
• DOI: 10.2217/pgs-2017-0176

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.