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CYP3A5

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https://www.readbyqxmd.com/read/28723731/the-combined-effect-of-cyp2b6-genotype-and-other-candidate-genes-on-a-steady-state-serum-concentration-of-methadone-in-opioid-maintenance-treatment
#1
Marianne K Kringen, Fatemeh Chalabianloo, Jean-Paul Bernard, Jørgen G Bramness, Espen Molden, Gudrun Høiseth
BACKGROUND: A considerable inter-individual variability in methadone pharmacokinetics is seen in patients on methadone maintenance treatment. The aim of this study was to clarify the impact of the reduced function CYP2B6*6 variant allele together with variants in other candidate genes on a steady-state methadone concentration in a naturalistic setting. METHODS: Information of methadone serum concentration, dose, age, gender and CYP2C9, CYP2C19, and CYP2D6 genotypes were collected from a routine therapeutic drug monitoring (TDM) database while variant alleles in CYP2B6 and CYP3A5 were retrospectively genotyped...
July 18, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28723497/pharmacogenomic-markers-of-targeted-therapy-toxicity-in-patients-with-metastatic-renal-cell-carcinoma
#2
Guillermo de Velasco, Kathryn P Gray, Lana Hamieh, Yuksel Urun, Hallie A Carol, Andre P Fay, Sabina Signoretti, David J Kwiatkowski, David F McDermott, Matthew Freedman, Mark M Pomerantz, Toni K Choueiri
BACKGROUND: Targeted therapy (TT) in metastatic renal cell carcinoma (mRCC) may be associated with a high rate of toxicity that undermines treatment efficacy and patient quality of life. Polymorphisms in genes involved in the pharmacokinetic pathways of TTs may predict toxicity. OBJECTIVE: To investigate whether selected single-nucleotide polymorphisms (SNPs) in three core genes involved in the metabolism and transport of sunitinib and the mTOR inhibitors everolimus and temsirolimus are associated with adverse events (AEs)...
December 15, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28704257/the-combination-of-cyp3a4-22-and-cyp3a5-3-single-nucleotide-polymorphisms-determines-tacrolimus-dose-requirement-after-kidney-transplantation
#3
Nuria Lloberas, Laure Elens, Ines Llaudó, Ariadna Padullés, Teun van Gelder, Dennis A Hesselink, Helena Colom, Franc Andreu, Joan Torras, Oriol Bestard, Josep M Cruzado, Salvador Gil-Vernet, Ron van Schaik, Josep M Grinyó
INTRODUCTION: Tacrolimus (Tac) has a narrow therapeutic window and shows large between-patient pharmacokinetic variability. As a result, over-immunosuppression and under-immunosuppression are frequently encountered in daily clinical practice. Unraveling the impact of genetic polymorphisms on Tac pharmacokinetics may help to refine therapy. In this study, the associations of single-nucleotide polymorphisms (SNPs) in drug-metabolizing enzymes (CYP3A) with Tac pharmacokinetics were investigated in renal transplant recipients...
July 12, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28700521/effect-of-cyp3a4-and-cyp3a5-genetic-polymorphisms-on-the-pharmacokinetics-of-sirolimus-in-healthy-chinese-volunteers
#4
Jing Zhang, Ying Dai, Zhihong Liu, Minxin Zhang, Chen Li, Dingxiong Chen, Hongtao Song
BACKGROUND: Sirolimus is a promising immunosuppressive drug for preventing the rejection of organ transplants. However, inter-individual variability in sirolimus pharmacokinetics causes adverse drug reactions, compromising therapeutic efficacy. Sirolimus is primarily metabolized by cytochrome CYP3A4 and CYP3A5. This study aimed to clarify the effect of CYP3A genetic polymorphisms, including the CYP3A4*1G and CYP3A5*3 polymorphisms, on the pharmacokinetics of sirolimus. METHODS: Thirty-one healthy Chinese volunteers were included in this study...
August 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28697165/association-of-cyp3a5-expression-and-vincristine-neurotoxicity-in-pediatric-malignancies-in-turkish-population
#5
Hülya Kayilioğlu, Ulker Kocak, Derya Kan Karaer, Emriye F Percin, Ertan Sal, Funda Tekkesin, Melek Isik, Nergiz Oner, Fatma B Belen, Ebru Yilmaz Keskin, Arzu Okur, Meryem Albayrak, Zuhre Kaya, Faruk G Pinarli, Idil Yenicesu, Ceyda Karadeniz, Aynur Oguz, Turkiz Gursel
Vincristine is a widely used chemotherapeutic agent in the treatment of childhood malignancies. Neuropathy is the most common adverse effect. CYP3A4 and CYP3A5 enzymes of cytochrome p450 enzyme system are responsible in vincristine metabolism. Genetic polymorphism may alter the vincristine metabolism and the neurotoxicity rate. In this study, distribution of CYP3A5 alleles among Turkish children with malignancies, relation between CYP3A5 genotype and neurotoxicity rates, as well as severity and duration of neuropathy and total vincristine doses were investigated...
July 10, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28686294/nfat-regulated-cytokine-gene-expression-during-tacrolimus-therapy-early-after-renal-transplantation
#6
Sara Bremer, Nils T Vethe, Morten Skauby, Margrete Kasbo, Elisabet D Johansson, Karsten Midtvedt, Stein Bergan
AIMS: Despite pharmacokinetic monitoring of calcineurin inhibitors, the long-term outcome after transplantation (Tx) is still hampered by the side effects of these drugs. The aim of this study was to characterize the nuclear factor of activated T cells (NFAT)-regulated gene expression as a potential pharmacodynamic biomarker for further individualization of tacrolimus (Tac) therapy. METHODS: In 29 renal allograft recipients samples were drawn once pre-Tx, and before and 1...
July 7, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28685716/gene-variations-of-sixth-complement-component-affecting-tacrolimus-metabolism-in-patients-with-liver-transplantation-for-hepatocellular-carcinoma
#7
Jian-Hua Liao, Chang-Can Li, Shao-Han Wu, Jun-Wei Fan, Hai-Tao Gu, Zhao-Wen Wang
BACKGROUND: Orthotopic liver transplantation (OLT) improves the prognosis of patients with hepatocellular carcinoma (HCC). Moreover, the complement system is a powerful immune effector that can affect liver function and process of liver cirrhosis. However, studies correlating the complement system with tacrolimus metabolism after OLT are scarce. In this study, the role of single nucleotide polymorphisms (SNPs) associated with the sixth complement component (C6) in tacrolimus metabolism was investigated during the early stages of liver transplantation...
July 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28678049/impact-of-abcb1-abcg2-and-cyp3a5-polymorphisms-on-plasma-trough-concentrations-of-apixaban-in-japanese-patients-with-atrial-fibrillation
#8
Satoshi Ueshima, Daiki Hira, Ryo Fujii, Yuuma Kimura, Chiho Tomitsuka, Takuya Yamane, Yohei Tabuchi, Tomoya Ozawa, Hideki Itoh, Minoru Horie, Tomohiro Terada, Toshiya Katsura
OBJECTIVES: During anticoagulant therapy, major bleeding is one of the most severe adverse effects. This study aimed to evaluate the relationships between ABCB1, ABCG2, and CYP3A5 polymorphisms and plasma trough concentrations of apixaban, a direct inhibitor of coagulation factor X. PATIENTS AND METHODS: A total of 70 plasma concentrations of apixaban from 44 Japanese patients with atrial fibrillation were analyzed. In these analyses, the plasma trough concentration/dose (C/D) ratio of apixaban was used as a pharmacokinetic index and all data were stratified according to the presence of ABCB1 (ABCB1 1236C>T, 2677G>T/A, and 3435C>T), ABCG2 (ABCG2 421C>A), and CYP3A5 (CYP3A5*3) polymorphisms...
July 3, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28676933/association-of-nr1i2-cyp3a5-and-abcb1-genetic-polymorphisms-with-variability-of-temsirolimus-pharmacokinetics-and-toxicity-in-patients-with-metastatic-bladder-cancer
#9
Litaty C Mbatchi, Matthieu Gassiot, Philippe Pourquier, Alejando Goberna, Hakim Mahammedi, Loic Mourey, Florence Joly, Serge Lumbroso, Alexandre Evrard, Nadine Houede
PURPOSE: Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor that exhibits antitumor activity in renal cell carcinoma and mantle cell lymphoma. The metabolism of temsirolimus and its active metabolite sirolimus mainly depends on cytochrome P450 3A4/5 (CYP3A4/A5) and the ABCB1 transporter. Differently from sirolimus, no pharmacogenetic study on temsirolimus has been conducted. Therefore, the aim of this pilot study was to identify genetic determinants of the inter-individual variability in temsirolimus pharmacokinetics and toxicity...
July 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28673292/effect-of-pharmacogenetics-on-plasma-lumefantrine-pharmacokinetics-and-malaria-treatment-outcome-in-pregnant-women
#10
Ritah F Mutagonda, Appolinary A R Kamuhabwa, Omary M S Minzi, Siriel N Massawe, Muhammad Asghar, Manijeh V Homann, Anna Färnert, Eleni Aklillu
BACKGROUND: Pregnancy has considerable effects on the pharmacokinetic properties of drugs used to treat uncomplicated Plasmodium falciparum malaria. The role of pharmacogenetic variation on anti-malarial drug disposition and efficacy during pregnancy is not well investigated. The study aimed to examine the effect of pharmacogenetics on lumefantrine (LF) pharmacokinetics and treatment outcome in pregnant women. METHODS: Pregnant women with uncomplicated falciparum malaria were enrolled and treated with artemether-lumefantrine (ALu) at Mkuranga and Kisarawe district hospitals in Coast Region of Tanzania...
July 3, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28666968/in-vitro-phase-i-metabolism-of-gamabufotalin-and-arenobufagin-reveal-the-effect-of-substituent-group-on-metabolic-stability
#11
Yujie Feng, Chao Wang, Xiangge Tian, Xiaokui Huo, Lei Feng, Chengpeng Sun, Guangbo Ge, Ling Yang, Jing Ning, Xiaochi Ma
Bufadienolides are a major class of bioactive compounds derived from amphibian skin secretion. Gamabufotalin (GB) and arenobufagin (AB) are among the top of the intensively investigated natural bufadienolides for their outstanding biological activities. This study aimed to characterize the phase I metabolism of GB and AB with respect to the metabolic profiles, enzymes involved, and catalytic efficacy, thereafter tried to reveal substituent effects on metabolism. Two mono-hydroxylated products of GB and AB were detected in the incubation mixtures, and they were accurately identified as 1- and 5-hydroxylated bufadienolides by NMR and HPLC-MS techniques...
June 27, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28655393/the-role-of-single-nucleotide-polymorphisms-of-cyp3a-and-abcb1-on-tacrolimus-predose-concentration-in-kidney-transplant-recipients
#12
Gregor Mlinšek, Vita Dolžan, Katja Goričar, Jadranka Buturović-Ponikvar, Miha Arnol
BACKGROUND: Tacrolimus has a narrow therapeutic drug window but high inter- and intrapatient variability. Our aim is to construct a model able to predict optimal maintenance tacrolimus predose concentration (C0) in kidney transplant patients. Here we present our study design and genotype and variant allele frequencies for the selected single nucleotide polymorphisms of genes involved in tacrolimus metabolism in our national cohort of kidney transplant recipients. METHODS: In the observational part of the study, we intend to determine allelic variants of CYP3A4, CYP3A5, and ABCB1 gene in a national cohort of 700 kidney transplants recipients...
June 28, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28646274/population-pharmacokinetic-modeling-of-diltiazem-in-chinese-renal-transplant-recipients
#13
Xiao-Feng Guan, Dai-Yang Li, Wen-Jun Yin, Jun-Jie Ding, Ling-Yun Zhou, Jiang-Lin Wang, Rong-Rong Ma, Xiao-Cong Zuo
BACKGROUND AND OBJECTIVES: Diltiazem is a benzothiazepine calcium blocker and widely used in renal transplant patients since it improves the level of tacrolimus or cyclosporine A concentration. Several population pharmacokinetic (PopPK) models had been established for cyclosporine A and tacrolimus but no specific PopPK model was established for diltiazem. The aim of the study is to develop a PopPK model for diltiazem in renal transplant recipients and provide relevant pharmacokinetic parameters of diltiazem for further pharmacokinetic interaction study...
June 23, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28642710/tacrolimus-updated-guidelines-through-poppk-modeling-how-to-benefit-more-from-cyp3a-pre-emptive-genotyping-prior-to-kidney-transplantation
#14
Jean-Baptiste Woillard, Michel Mourad, Michael Neely, Arnaud Capron, Ron H van Schaik, Teun van Gelder, Nuria Lloberas, Dennis A Hesselink, Pierre Marquet, Vincent Haufroid, Laure Elens
Tacrolimus (Tac) is a profoundly effective immunosuppressant that reduces the risk of rejection after solid organ transplantation. However, its use is hampered by its narrow therapeutic window along with its highly variable pharmacological (pharmacokinetic [PK] and pharmacodynamic [PD]) profile. Part of this variability is explained by genetic polymorphisms affecting the metabolic pathway. The integration of CYP3A4 and CY3A5 genotype in tacrolimus population-based PK (PopPK) modeling approaches has been proven to accurately predict the dose requirement to reach the therapeutic window...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28637770/analgesia-and-opioids-a-pharmacogenetics-shortlist-for-implementation-in-clinical-practice
#15
REVIEW
Maja Matic, Saskia N de Wildt, Dick Tibboel, Ron H N van Schaik
BACKGROUND: The use of opioids to alleviate pain is complicated by the risk of severe adverse events and the large variability in dose requirements. Pharmacogenetics (PGx) could possibly be used to tailor pain medication based on an individual's genetic background. Many potential genetic markers have been described, and the importance of genetic predisposition in opioid efficacy and toxicity has been demonstrated in knockout mouse models and human twin studies. Such predictors are especially of value for neonates and young children, in whom the assessment of efficacy or side effects is complicated by the inability of the patient to communicate this properly...
July 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28621555/slc28a3-rs7853758-as-a-new-biomarker-of-tacrolimus-elimination-and-new-onset-hypertension-in-chinese-liver-transplantation-patients
#16
Yuan Liu, Tao Zhang, Changcan Li, Ling Ye, Haitao Gu, Lin Zhong, Hongcheng Sun, Yahuang Sun, Zhihai Peng, Junwei Fan
AIM: The effect of SLC28A3 on tacrolimus disposition and new-onset hypertension (NOHP) after liver transplantation (LT) remains unclear. Methodology & results: A total of 169 patients in two cohorts from the China Liver Transplant Registry database were included. Rs7853758 in recipients'SLC28A3 could predict tacrolimus pharmacokinetics in two sets. The model of donors' CYP3A5 rs776746 and recipients' CYP3A4 rs2242480 could predict tacrolimus metabolism at week 1 and the model of donors' CYP3A5 rs776746, recipients' CYP3A4 rs2242480, recipients' SLC28A3 rs7853758 and hemoglobin could predict tacrolimus disposition at weeks 2, 3 and 4...
June 16, 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/28618035/population-pharmacokinetics-of-imatinib-in-nigerians-with-chronic-myeloid-leukemia-clinical-implications-for-dosing-and-resistance
#17
Babatunde Ayodeji Adeagbo, Tiwalade Adewale Olugbade, Muheez Alani Durosinmi, Rahman Ayodele Bolarinwa, Kayode Ogungbenro, Oluseye Oladotun Bolaji
Imatinib, a tyrosine kinase inhibitor, is the drug of choice for the treatment of chronic myeloid leukemia in Nigeria. Several studies have established interindividual and interpopulation variations in imatinib disposition although no pharmacokinetic study have been conducted in an African population since the introduction of the drug. This study explored a population pharmacokinetic approach to investigate the disposition of imatinib in Nigerians and examined the involvement of some covariates including genetic factors in the variability of the drug disposition with a view to optimize the use of the drug in this population...
June 15, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28611384/the-correlation-between-the-expression-of-genes-involved-in-drug-metabolism-and-the-blood-level-of-tacrolimus-in-liver-transplant-receipts
#18
Jianhai Wang, Keqiu Li, Xiaoning Zhang, Dahong Teng, Mingyan Ju, Yaqing Jing, Yuxia Zhao, Guang Li
Immunosuppressive medications, such as tacrolimus and mycophenolate mofetil, are commonly used for reducing the risk of organ rejection in receipts of allogeneic organ transplant. The optimal dosages of these drugs are required for preventing rejection and avoiding toxicity to receipts. This study aimed to identify the correlation between the expression profiling of genes involved in drug metabolism and the blood level of tacrolimus in liver transplant receipts. Sixty-four liver transplant receipts were enrolled in this retrospective study...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28606510/in-vitro-inhibitory-mechanisms-and-molecular-docking-of-1-s-1-acetoxychavicol-acetate-on-human-cytochrome-p450-enzymes
#19
A K M Mahmudul Haque, Kok Hoong Leong, Yoke Lin Lo, Khalijah Awang, Noor Hasima Nagoor
BACKGROUND: The compound, 1'-S-1'-acetoxychavicol acetate (ACA), isolated from the rhizomes of a Malaysian ethno-medicinal plant, Alpinia conchigera Griff. (Zingiberaceae), was previously shown to have potential in vivo antitumour activities. In the development of a new drug entity, potential interactions of the compound with the cytochrome P450 superfamily metabolizing enzymes need to be ascertain. PURPOSE: The concomitant use of therapeutic drugs may cause potential drug-drug interactions by decreasing or increasing plasma levels of the administered drugs, leading to a suboptimal clinical efficacy or a higher risk of toxicity...
July 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28605053/prevalence-of-cyp3a5-genomic-variances-and-their-impact-on-tacrolimus-dosing-requirements-among-kidney-transplant-recipients-in-eastern-north-carolina
#20
Angela Q Maldonado, Tomefa Asempa, Suzanne Hudson, Lorita M Rebellato
STUDY OBJECTIVE: To assess the prevalence of CYP3A5 genomic variances and their impact on tacrolimus dosing requirements among kidney transplant recipients in eastern North Carolina. DESIGN: Single-center, retrospective cohort study. SETTING: Large tertiary care medical center. PATIENTS: A total of 162 adults who received a kidney transplant between March 1, 2013, and February 28, 2015, and received oral tacrolimus as part of their maintenance immunosuppression; of these patients, 85 patients expressed a genotype with a CYP3A5*1 variant (CYP3A5*1 group), and 77 patients expressed genotypes with other CYP3A5 variants (nonexpressor group)...
June 12, 2017: Pharmacotherapy
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