Eur J Clin Pharmacol 2007 Jun 3;63(6):547-54. Epub 2007 Apr 3.
Department of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
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J Acquir Immune Defic Syndr 2010 Dec;55(5):536-49
Department of Pharmacology & Therapeutics, Trinity College, Dublin, Ireland.
Background: Antiretroviral therapy including HIV protease inhibitors and nonnucleoside reverse transcriptase inhibitors can both inhibit and induce expression of cytochrome P450s, potentially leading to drug interactions. However, information is lacking on the impact of genetic polymorphism on this interaction.
Methods: This study examines the prevalence of 33 polymorphisms in NR1I2 (pregnane X receptor [PXR]), CYP3A4, and CYP2B6 in 1013 white and sub-Saharan African patients with HIV; explores the inductive ability of 16 antiretrovirals on CYP3A4 and CYP2B6 promoter activity through nuclear receptors PXR and constitutive androstane receptor (CAR); and evaluates the influence of naturally occurring PXR genetic variants on antiretroviral activation. Read More
Acta Pharmacol Sin 2013 Apr 18;34(4):555-60. Epub 2013 Mar 18.
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Aim: Cyclosporine requires close therapeutic drug monitoring because of its narrow therapeutic index and marked inter-individual pharmacokinetic variation. In this study, we investigated the associations of CYP3A4, CYP3A5, ABCB1, NFKB1, and NR1I2 polymorphisms with cyclosporine concentrations in Chinese renal transplant recipients in the early period after renal transplantation.
Methods: A total of 101 renal transplant recipients receiving cyclosporine were genotyped for CYP3A4(*)1G, CYP3A5(*)3, ABCB1 C1236T, G2677T/A, C3435T, NFKB1 -94 ins/del ATTG, and NR1I2 polymorphisms. Read More
Antimicrob Agents Chemother 2010 Dec 4;54(12):5242-50. Epub 2010 Oct 4.
Department of Pharmacology and Therapeutics, University of Liverpool, 70 Pembroke Place, Liverpool L69 3GF, United Kingdom.
Atazanavir (ATV) plasma concentrations are influenced by CYP3A4 and ABCB1, which are regulated by the pregnane X receptor (PXR; NR1I2). PXR expression is correlated with CYP3A4 in liver in the absence of enzyme inducers. The PXR single nucleotide polymorphism (SNP) 63396C→T (rs2472677) alters PXR expression and CYP3A4 activity in vitro, and we previously showed an association of this polymorphism with unboosted ATV plasma concentrations. Read More
Steroids 2008 Oct 11;73(11):1052-9. Epub 2008 Apr 11.
Department of Pharmacy, Akita University Hospital, Akita, 1-1-1 Hondo, Akita 010-8543, Japan.
The objective of this study was to evaluate whether genetic polymorphisms of CYP3A5 (A6986G, CYP3A5*3), ABCB1 (C1236T, G2677T/A, C3435T) and NR1I2 (A7635G) significantly impact the pharmacokinetics of prednisolone in renal transplant recipients. Ninety-five recipients were given repeated doses of triple therapy immunosuppression consisting of prednisolone, tacrolimus and mycophenolate mofetil. Twenty-eight days after renal transplantation, plasma prednisolone concentrations were measured by high-performance liquid chromatography. Read More