Read by QxMD icon Read


Lucy Chen, G V Ramesh Prasad
Tacrolimus is a commonly used immunosuppressant after kidney transplantation. It has a narrow therapeutic range and demonstrates wide interindividual variability in pharmacokinetics, leading to potential underimmunosuppression or toxicity. Genetic polymorphism in CYP3A5 enzyme expression contributes to differences in tacrolimus bioavailability between individuals. Individuals carrying one or more copies of the wild-type allele *1 express CYP3A5, which increases tacrolimus clearance. CYP3A5 expressers require 1...
2018: Pharmacogenomics and Personalized Medicine
Ida Robertsen, Jean Debord, Anders Åsberg, Pierre Marquet, Jean-Baptiste Woillard
BACKGROUND AND OBJECTIVE: Intracellular exposure of everolimus may be a better marker of therapeutic effect than trough whole blood concentrations. We aimed to develop pharmacokinetic population models and Bayesian estimators based on a limited sampling strategy for estimation of dose interval exposures of everolimus in whole blood and peripheral blood mononuclear cells (PBMCs) in renal transplant recipients. METHODS: Full whole blood and PBMC concentration-time profiles of everolimus were obtained from 12 stable renal transplant recipients on two different occasions, 4 weeks apart...
March 20, 2018: Clinical Pharmacokinetics
Naoki Komine, Shigeru Satoh, Mitsuru Saito, Kazuyuki Numakura, Takamitsu Inoue, Hiroshi Tsuruta, Shintaro Narita, Atsushi Komatsuda, Hiroshi Nanjo, Hideaki Kagaya, Takenori Niioka, Masatomo Miura, Yoko Mitobe, Tomonori Habuchi
The impact of CYP3A5 polymorphisms on clinical outcomes is controversial. The present study investigated the impact of CYP3A5 genetic differences on the development of interstitial fibrosis (IF) from 0 h to 1 year post-transplantation in biopsy sections from 96 living kidney recipients under the same target trough regimen of tacrolimus. The relationships between CYP3A5 polymorphisms and long-term graft function and death-censored graft survival were also examined. A quantitative analysis of IF was performed using computer-assisted imaging on virtual slides...
March 14, 2018: International Immunopharmacology
Hideaki Kagaya, Takenori Niioka, Mitsuru Saito, Takamitsu Inoue, Kazuyuki Numakura, Ryohei Yamamoto, Yumiko Akamine, Tomonori Habuchi, Shigeru Satoh, Masatomo Miura
While tacrolimus and everolimus have common metabolic pathways through CYP3A4/5, tacrolimus is metabolized solely by CYP3A4 in recipients with the CYP3A5*3 / *3 . The purpose of this study was to evaluate how the area under the blood concentration-time curves (AUC) of tacrolimus could be predicted based on CYP3A5 genotype and the AUC of everolimus in renal transplant patients taking both drugs. The dose-adjusted AUC (AUC/D) of tacrolimus and everolimus were calculated at one month and one year after transplantation...
March 16, 2018: International Journal of Molecular Sciences
Daohua Shi, Tiancheng Xie, Jie Deng, Peiguang Niu, Weizhen Wu
PURPOSE: We intend to investigate the association between tacrolimus-induced new-onset diabetes after transplantation (NODAT) and polymorphisms of CYP3A4, CYP3A5, ATP-binding cassette transporter sub-family C member 8 (ABCC8), and glucokinase (GCK) in renal transplant recipients. METHODS: Polymorphisms of CYP3A4 *18B, CYP3A5 *3, ABCC8 T-3C, and GCK G-30A were genotyped in 169 renal transplant recipients. Trough concentrations of tacrolimus were detected by an ELISA kit...
March 15, 2018: European Journal of Clinical Pharmacology
Suwasin Udomkarnjananun, Natavudh Townamchai, Pajaree Chariyavilaskul, Kroonpong Iampenkhae, Krit Pongpirul, Boonchoo Sirichindakul, Kamol Panumatrassamee, Jakapat Vanichanan, Yingyos Avihingsanon, Somchai Eiam-Ong, Kearkiat Praditpornsilpa
BACKGROUND: Tacrolimus is mainly metabolized by cytochrome P450 3A5 (CYP3A5), which is expressed in the liver. However, CYP3A5 is also expressed in the kidney tissue and may contribute to local tacrolimus clearance in the kidney allograft. We aimed to evaluate the association between the allograft CYP3A5 genotype and transplant outcomes. METHODS: We conducted a retrospective cohort study at the King Chulalongkorn Memorial Hospital, Thailand, comparing 2 groups of donor and recipient CYP3A5 genotypes, the expressor (*1/*1 and *1/*3) and the non-expressor (*3/*3)...
March 14, 2018: American Journal of Nephrology
Tianyi Xia, Sang Zhu, Yan Wen, Shouhong Gao, Mingming Li, Xia Tao, Feng Zhang, Wansheng Chen
Background: Nephrotoxicity of calcineurin inhibitors (CNIs) is the major concern for long-term allograft survival despite its predominant role in current immunosuppressive regime after renal transplantation. CNI nephrotoxicity is multifactorial with demographic, environmental, and pharmacogenetic flexibility, whereas studies indicating risk factors for CNI nephrotoxicity obtained incomplete or conflicting results. Methods: A systematic review and meta-analysis of risk factors for CNI nephrotoxicity was performed on all retrieved studies through a comprehensive research of network database...
2018: Drug Design, Development and Therapy
Dong-Feng Zhang, Guo-Xiang Hao, Chun-Zhen Li, Yan-Jun Yang, Fu-Juan Liu, Ling Liu, Xiao-Ying Yuan, Rui-Hong Li, Lei Dong, Qian Dong, Evelyne Jacqz-Aigrain, Wei Zhao
BACKGROUND: Tacrolimus is used off-label in the treatment of Henoch-Schönlein purpura nephritis (HSPN) in children, with limited evidence-based data. Based on clinical empirical experience and mechanism of action, tacrolimus might be promoted as treatment for childhood HSPN. The objectives of this pilot study were to assess its effectiveness and safety, and to explore the potential impact of CYP3A5 genotype. METHODS: Children with HSPN receiving tacrolimus as empirical treatment were included in this prospective, observational study...
March 13, 2018: Archives of Disease in Childhood
Ryoma Igarashi, Takamitsu Inoue, Nobuhiro Fujiyama, Norihiko Tsuchiya, Kazuyuki Numakura, Hideaki Kagaya, Mitsuru Saito, Shintaro Narita, Shigeru Satoh, Takenori Niioka, Masatomo Miura, Tomonori Habuchi
Axitinib is a potent second-line molecular-targeted agent for metastatic renal cell carcinoma (mRCC). Axitinib pharmacokinetics and its relation with genetic polymorphisms were evaluated to predict the adverse events (AEs) and efficacy of axitinib. We analyzed 46 patients with mRCC who were treated with axitinib. The plasma axitinib level was measured at 0, 2, 4, 8, and 12 h after administration (C0 , C2 , C4 , C8 , and C12 ; ng/mL) on day 7 of the treatment. Genetic polymorphisms related to axitinib pharmacokinetics, including SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCG2, CYP2C19, CYP3A5, and UGT1A1, were analyzed...
March 9, 2018: Medical Oncology
Sufeng Zhou, Mingxue Tao, Yuanyuan Wang, Lu Wang, Lijun Xie, Juan Chen, Yuqing Zhao, Yun Liu, Hongwen Zhang, Ning Ou, Guangji Wang, Feng Shao, Jiye Aa
1. The aim of this analysis was to explore the influence of CYP3A4*1G and CYP3A5*3 polymorphisms on the pharmacokinetics of tylerdipine in healthy Chinese subjects. 2. A total of 64 and 63 healthy Chinese subjects were included and identified as the genotypes of CYP3A4*1G and CYP3A5*3, respectively. Plasma samples were collected for up to 24 h post-dose to characterize the pharmacokinetic profile following single oral dose of the drug (5, 15, 20, 25, 30 mg). Plasma levels were measured by a high-performance liquid chromatography-mass spectrometry (LC-MS/MS)...
March 9, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Nikhat Saba, Alpana Seal
Vinca alkaloids are chemotherapeutic agents used in the treatment of both pediatric and adult cancer patients. Cytochrome P450 3A5 (CYP3A5) is 9- to 14-fold more efficient at clearing vincristine than cytochrome P450 3A4 (CYP3A4) is. However, patients who express an inactive form of the polymorphic CYP3A5 enzyme suffer from severe neurotoxicity during vincristine treatment, resulting in chemotherapy failure. Previous studies have found that the addition of new features to the parent drug can enhance its binding affinity to tubulin manyfold and could therefore yield novel anticancer drugs...
March 4, 2018: Journal of Molecular Modeling
Łucja Fiszer-Maliszewska, Łukasz Łaczmański, Aneta Dolińska, Maria Jagas, Ewelina Kołodziejska, Magdalena Jankowska, Piotr Kuśnierczyk
BACKGROUND/AIM: Ovarian cancer is a lethal gynecological malignancy, with 5-year survival of only about one third of patients. The ABCB1 gene encodes the P-glycoprotein which is one of the multidrug efflux pumps. Its decreased activity may result in multidrug resistance of cancer cells. Drug-metabolizing enzymes Cyp3A4 and Cyp3A5 may affect success of chemotherapy. In this study we attempted to examine the effects of 12 single nucleotide polymorphisms (SNPs) of the ABCB1 gene and one SNP in each of CYP3A4 and CYP3A5 genes on the incidence of ovarian cancer in Polish women and their response to treatment...
March 2018: Anticancer Research
Kanakaiah Thota, K Prasad, Mandava V Basaveswara Rao
Background: Breast cancer is the most common cancer among women worldwide. Tamoxifen (TAM), a selective estrogen receptor modulator, is widely used in its treatment. TAM is metabolized by cytochrome P450 (CYP450) enzymes, including CYP2D6, CYP3A5 and CYP2C19, whose genetic variations may have clinicopathological importance. However, reports on the association of various P450 polymorphisms with certain cancers are contradictory. Methods: We here investigated whether the prevalence of the four most common polymorphism in the CYP2D6*4 (G1934A), CYP2D6*10 (C188T), CYP3A5*3 and CYP2C19*2 alleles has any link with breast cancer using genomic DNA and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis...
February 26, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Agnieszka Prytuła, Teun van Gelder
The calcineurin inhibitor tacrolimus, cornerstone of most immunosuppressive regimens, is a drug with a narrow therapeutic window: underexposure can lead to allograft rejection and overexposure can result in an increased incidence of infections, toxicity and malignancies. Tacrolimus is metabolised in the liver and intestine by the cytochrome P450 3A (CYP3A) isoforms CYP3A4 and CYP3A5. This review focusses on the clinical aspects of tacrolimus pharmacodynamics, such as efficacy and toxicity. Factors affecting tacrolimus pharmacokinetics, including pharmacogenetics and the rationale for routine CYP3A5*1/*3 genotyping in prospective paediatric renal transplant recipients, are also reviewed...
February 26, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Elaine Tseng, Gwendolyn D Fate, Gregory S Walker, Theunis C Goosen, R Scott Obach
Maraviroc (MVC) is an CCR5 co-receptor antagonist indicated in combination with other antiretroviral agents for the treatment of CCR5-tropic human immunodefinciency virus-1 (HIV-1) infection. In this study, the metabolism of MVC was investigated in human liver microsomes to delineate the relative roles of CYP3A4 and CYP3A5. MVC is metabolized to five hydroxylated metabolites, all of which were biosynthesized and identified using mass and NMR spectroscopy. The sites of metabolism were the 2- and 3-positions of the 4,4-difluorocyclohexyl moiety and the methyl of the triazole moiety...
February 23, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Rommel G Tirona, Zahra Kassam, Ruth Strapp, Mala Ramu, Catherine Zhu, Melissa Liu, Ute I Schwarz, Richard B Kim, Bandar Al-Judaibi, Melanie D Beaton
There is little known about the impact of nonalcoholic fatty liver disease (NAFLD) on drug metabolism and transport. We examined the pharmacokinetics of oral apixaban (2.5 mg) and rosuvastatin (5 mg) when administered simultaneously in subjects with magnetic resonance imaging-confirmed NAFLD (N=22) and healthy controls (N=12). The areas under the plasma concentration-time curve (AUC0-12 ) for apixaban were not different between control and NAFLD subjects (671 and 545 ng/mL×hr, respectively; P=0.15). In multivariable linear regression analyses, only participant weight but not NAFLD, age or SLCO1B1/ABCG2/CYP3A5 genotypes, was associated with apixaban and rosuvastatin AUC0-12 (P<0...
February 22, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Satoshi Ueshima, Daiki Hira, Yuuma Kimura, Ryo Fujii, Chiho Tomitsuka, Takuya Yamane, Yohei Tabuchi, Tomoya Ozawa, Hideki Itoh, Seiko Ohno, Minoru Horie, Tomohiro Terada, Toshiya Katsura
AIMS: This study aimed to analyse the effects of genetic polymorphisms in drug transporters and metabolising enzymes, and clinical laboratory data on the pharmacokinetic parameters of apixaban. METHODS: Data were collected from 81 Japanese patients with atrial fibrillation. Pharmacogenomic data were stratified by ABCB1, ABCG2, and CYP3A5 polymorphisms. The pharmacokinetic profile of apixaban was described by a one-compartment model with first-order absorption. Population pharmacokinetic analysis was conducted using non-linear mixed effect modelling (NONMEM™) program...
February 19, 2018: British Journal of Clinical Pharmacology
Jianyu Liu, Yabo Ouyang, Dexi Chen, Bo Yao, Dongdong Lin, Zhiqiang Li, Yunjin Zang, Huan Liu, Xiaoyue Fu
The immunosuppressant drug tacrolimus (Tac) used for the prevention of immunological rejection is a metabolic substrate of cytochrome P450 enzymes. This study was designed to evaluate the short-term and long-term potential influence of single-nucleotide polymorphisms (SNPs) in CYP450 genes of liver transplant (LT) recipients as well as the donors on individual pharmacological effects of Tac and to guide individualized-medication from the perspective of pharmacogenomics. Twenty-one SNPs of the CYP450 gene were genotyped for both recipients and donors in 373 LT patients receiving Tac-based immunosuppressants...
February 14, 2018: International Immunopharmacology
Geik Yong Ang, Choo Yee Yu, Richard Johari James, Aminuddin Ahmad, Thuhairah Abdul Rahman, Fadzilah Mohd Nor, Syahrul Azlin Shaari, Adzrool Idzwan Ismail, Lay Kek Teh, Mohd Zaki Salleh
CYP3A5 is the predominant subfamily of biotransformation enzymes in the liver and the genetic variations in CYP3A5 are an important determinant of interindividual and interethnic differences in CYP3A-mediated drug disposition and response. This study aims to investigate the genetic polymorphisms of CYP3A5 among the Orang Asli in Peninsular Malaysia using next generation sequencing platform. Genomic DNAs were extracted from blood samples of the three main Orang Asli tribes and whole-genome sequencing was performed...
February 15, 2018: Annals of Human Biology
Shuaibing Liu, Ling Xue, Xiangfen Shi, Zhiyong Sun, Zhenfeng Zhu, Xiaojian Zhang, Xin Tian
BACKGROUND: Ticagrelor, the first reversible P2Y12 receptor antagonist, exhibits faster onset and offset of antiplatelet effects and more consistent platelet inhibition than clopidogrel in both healthy subjects and patients with stable coronary artery disease. OBJECTIVE: The objectives of this study were to establish a population pharmacokinetics (PK) and pharmacodynamics (PD) model of ticagrelor and to provide a theoretical basis for the optimization of ticagrelor treatment in clinic...
February 13, 2018: European Journal of Clinical Pharmacology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"