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https://www.readbyqxmd.com/read/27858915/genetic-polymorphisms-of-cyp3a4-among-chinese-patients-with-steroid-induced-osteonecrosis-of-the-femoral-head
#1
Yuan Wang, Xiuling Li, Yaoyu Gao, Zhi Li, Lidong Yu, Qingbo Meng, Li Sun, Jianzhong Wang
BACKGROUND: Steroid therapy has been an important reason of nontraumatic osteonecrosis of the femoral head (ONFH). Steroids are metabolized by hepatic cytochrome P4503A, a low endogenous activity of this enzyme can contribute to the pathogenesis of ONFH. The aim of this study was to investigate the associations of polymorphisms of cytochrome P4503A4 (CYP3A4) gene with steroid-induced ONFH in Chinese patients. METHODS: A total of 150 steroid-induced ONFH patients and 250 healthy controls were enrolled...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27789970/pharmacogenetic-polymorphism-as-an-independent-risk-factor-for-frequent-hospitalizations-in-older-adults-with-polypharmacy-a-pilot-study
#2
Joseph Finkelstein, Carol Friedman, George Hripcsak, Manuel Cabrera
Pharmacogenetic testing identifies genetic biomarkers that are predictive of individual sensitivity to particular drugs. A significant proportion of medications that are widely prescribed for older adults are metabolized by enzymes that are encoded by highly polymorphic genes. Pharmacogenetic testing is increasingly used to optimize the medication regimen; however, its potential in older adults with polypharmacy has not been systematically explored. Following the initial case-series study, this study hypothesized that frequently hospitalized older adults with polypharmacy have higher frequency of pharmacogenetic polymorphism as compared to older adults with polypharmacy who are rarely admitted to a hospital...
2016: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/27619152/a-review-of-factors-explaining-variability-in-fentanyl-pharmacokinetics-focus-on-implications-for-cancer-patients
#3
REVIEW
Evelien J M Kuip, Maarten L Zandvliet, Stijn L W Koolen, Ron H J Mathijssen, Carin C D van der Rijt
Fentanyl is a strong opioid that is available for various administration routes, and which is widely used to treat cancer-related pain. Many factors influence the fentanyl pharmacokinetics leading to a wide inter- and intrapatient variability. This systematic review summarizes multiple studied factors that potentially influence fentanyl pharmacokinetics with a focus on implications for cancer patients. The use of CYP3A4 inhibitors and inducers, impaired liver function, and heating of the patch potentially influence fentanyl pharmacokinetics in a clinically relevant way...
September 12, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27264955/stat5a-and-stat5b-have-opposite-correlations-with-drug-response-gene-expression
#4
V Lamba, B Jia, F Liang
INTRODUCTION: STAT5A and STAT5B are important transcription factors that play a key role in regulation of several important physiological processes including proliferation, survival, mediation of responses to cytokines and in regulating gender differences in drug response genes such as the hepatic cytochrome P450s (CYPs) that are responsible for a large majority of drug metabolism reactions in the human body. STAT5A and STAT5b have a high degree of sequence homology and have been reported to have largely similar functions...
June 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27107788/gender-difference-in-prescription-opioid-abuse-a-focus-on-oxycodone-and-hydrocodone
#5
Manuela Graziani, Robert Nisticò
Several data gathered in the last decade indicate an increase of abuse of prescription opioid drugs oxycodone (OXY) and hydrocodone (HYDRO) in women. However, to date there are no conclusive evidences investigating the gender-dependent abuse liability of prescription opioids. This study aims to supply a specific focus on women's data through a selective summary of the literature analyzing gender differences in the pharmacokinetic and pharmacodynamic dimension of OXY and HYDRO. Findings from this study suggest that the majority of OXY and HYDRO pharmacokinetic and pharmacodynamic effects do not differ according to gender, though confirming a significant difference in the incidence of adverse effects as demonstrated by the increased gastrointestinal adverse reactions in female subjects...
April 20, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/26981194/complexity-of-vitamin-e-metabolism
#6
REVIEW
Lisa Schmölz, Marc Birringer, Stefan Lorkowski, Maria Wallert
Bioavailability of vitamin E is influenced by several factors, most are highlighted in this review. While gender, age and genetic constitution influence vitamin E bioavailability but cannot be modified, life-style and intake of vitamin E can be. Numerous factors must be taken into account however, i.e., when vitamin E is orally administrated, the food matrix may contain competing nutrients. The complex metabolic processes comprise intestinal absorption, vascular transport, hepatic sorting by intracellular binding proteins, such as the significant α-tocopherol-transfer protein, and hepatic metabolism...
February 26, 2016: World Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26924289/prediction-of-tacrolimus-metabolism-and-dosage-requirements-based-on-cyp3a4-phenotype-and-cyp3a5-3-genotype-in-chinese-renal-transplant-recipients
#7
Xi Luo, Li-jun Zhu, Ning-fang Cai, Li-yun Zheng, Ze-neng Cheng
AIM: To examine how the endogenous CYP3A4 phenotype and CYP3A5(*)3 genotype of Chinese renal transplant recipients influenced the dose-corrected trough concentration (C0/D) and weight-corrected daily dose (D/W) of tacrolimus. METHODS: A total of 101 medically stable kidney transplant recipients were enrolled, and their blood and urine samples were gathered. The endogenous CYP3A4 phenotype was assessed by the ratio of 6β-hydroxycortisol and 6β-hydroxycortisone to cortisol and cortisone in urine...
April 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/26891871/impact-of-cyp3a4-1g-allele-on-clinical-pharmacokinetics-and-pharmacodynamics-of-clopidogrel
#8
Dorota Danielak, Marta Karaźniewicz-Łada, Karolina Wiśniewska, Piotr Bergus, Paweł Burchardt, Anna Komosa, Franciszek Główka
BACKGROUND AND OBJECTIVES: Resistance to the antiplatelet treatment with clopidogrel has both genetic and non-genetic causes. Polymorphic variants of cytochrome P450 3A4 isoenzyme involved in the bioactivation of clopidogrel might have an influence on responsiveness to the drug. The aim of this study was to evaluate the influence of CYP3A4*1G (IVS10+12G>A, rs2242480) on the pharmacokinetics and pharmacodynamics of clopidogrel. METHODS: CYP3A4*1G polymorphism was determined in a group of 82 patients undergoing percutaneous coronary intervention and taking 75 mg of clopidogrel daily...
February 18, 2016: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/26765458/risks-of-adverse-events-following-coprescription-of-statins-and-calcium-channel-blockers-a-nationwide-population-based-study
#9
Yi-Chun Wang, Tsung-Cheng Hsieh, Chu-Lin Chou, Jung-Lun Wu, Te-Chao Fang
Some statins (simvastatin, lovastatin, and atorvastatin) are metabolized by cytochrome P450s 3A4 (CYP3A4). Inhibitors of CYP3A4 including some calcium channel blockers (CCBs) might increase statin blood concentration, owing to drug-drug interactions. Risk of adverse events such as acute kidney injury might occur following the coprescription of CYP3A4-metabolized statins and CCBs that inhibit CYP3A4.This was a population-based cohort study. The study analyzed data of patients treated between 1997 and 2011, retrieved from Taiwan's National Health Insurance database...
January 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/26727625/perampanel-serum-concentrations-in-adults-with-epilepsy-effect-of-dose-age-sex-and-concomitant-anti-epileptic-drugs
#10
Philip N Patsalos, Marilia Gougoulaki, Josemir W Sander
BACKGROUND: Perampanel (PMP), a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist, is a novel anti-epileptic drug (AED) licensed for the adjunctive treatment of focal and generalized epilepsy. There is limited information on PMP's pharmacokinetics and drug interaction characteristics with concomitant AEDs. We have investigated the effects of PMP dose, age, sex, and coprescribed AEDs on serum PMP concentrations. METHODS: We used the database of a therapeutic drug monitoring unit at a tertiary epilepsy referral center to identify patients who had PMP as part of their treatment and extracted clinical information from their medical notes...
June 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/26622646/effect-of-cyp2c19-and-cyp3a4-gene-polymorphisms-on-the-efficacy-of-bortezomib-based-regimens-in-patients-with-multiple-myeloma
#11
Weiwei Zhou, Guangyu An, Yuan Jian, Huan Guo, Wenming Chen
Bortezomib is used to treat patients with multiple myeloma. It is primarily metabolized by the enzyme cytochrome P450 (CYP). Variations in the capacity of bortezomib metabolism affect the treatment outcomes and the side-effects experienced by patients. In the present study, polymorphisms in the CYP3A4 and CYP2C19 genes were analyzed by polymerase chain reaction in 56 newly-diagnosed patients with multiple myeloma. The polymorphisms analyzed included the c.681G>A, c.636G>A and c.-806C>T polymorphisms of CYP2C19...
August 2015: Oncology Letters
https://www.readbyqxmd.com/read/26088794/cyp3a4-1g-genetic-polymorphism-influences-metabolism-of-fentanyl-in-human-liver-microsomes-in-chinese-patients
#12
Jing-Jing Yuan, Jun-Kai Hou, Wei Zhang, Yan-Zi Chang, Zhi-Song Li, Zong-Yu Wang, Ying-Ying Du, Xiao-Jing Ma, Li-Rong Zhang, Quan-Cheng Kan, Keith A Candiotti
PURPOSE: This study aimed to investigate whether CYP3A4*1G genetic polymorphism influences the metabolism of fentanyl in human liver microsomes in Chinese patients. METHODS: The human liver microsomes were obtained from 88 hepatobiliary surgery patients who accepted liver resection surgery in this study. A normal liver sample (confirmed by the Department of Pathology) was taken from the outer edge of the resected tissue. The metabolism of fentanyl in human liver microsomes was studied...
2015: Pharmacology
https://www.readbyqxmd.com/read/26011058/sunitinib-ibuprofen-drug-interaction-affects-the-pharmacokinetics-and-tissue-distribution-of-sunitinib-to-brain-liver-and-kidney-in-male-and-female-mice-differently
#13
Christine Li Ling Lau, Sook Tyng Chan, Manimegahlai Selvaratanam, Hui Wen Khoo, Adeline Yi Ling Lim, Pilar Modamio, Eduardo L Mariño, Ignacio Segarra
Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated...
August 2015: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/25992585/polymorphisms-in-cyp1b1-cyp3a5-gstt1-and-sult1a1-are-associated-with-early-age-acute-leukemia
#14
Bruno Almeida Lopes, Mariana Emerenciano, Bruno Alves Aguiar Gonçalves, Tállita Meciany Vieira, Ana Rossini, Maria S Pombo-de-Oliveira
Based on observational studies, early age leukemia (EAL) was associated with maternal hormone exposure during pregnancy. We studied the association between genetic polymorphisms of estrogen metabolism and EAL. Using data from the Brazilian Collaborative Study Group of Infant Acute Leukemia (2000-2012), 350 cases and 404 age-matched controls and 134 mothers of cases and controls were genotyped to explore polymorphisms in genes of the estrogen metabolism pathway: CYP1B1 (c.1294C>G, rs1056836), CYP3A4 (c.-392A>G, rs2740574), CYP3A5 (c...
2015: PloS One
https://www.readbyqxmd.com/read/25976223/cyp3a4%C3%A2-18b-and-cyp3a5%C3%A2-3-polymorphisms-contribute-to-pharmacokinetic-variability-of-cyclosporine-among-healthy-chinese-subjects
#15
COMPARATIVE STUDY
Xing-ru Tao, Xiu-yuan Xia, Jing Zhang, Lian-ying Tong, Wei Zhang, Xin Zhou, Zhi-Hong Liu, Hong-tao Song
AIM: Cyclosporine is an immunosuppressant drug used to prevent allograft rejection. It is metabolized by CYP3A4 and CYP3A5, has a narrow therapeutic index, and variable pharmacokinetics. Here, we investigated whether CYP3A5∗3 and CYP3A4∗18B polymorphisms contribute to inter-individual pharmacokinetic variability in healthy subjects. PATIENTS AND METHODS: Fifty-six healthy Chinese subjects were enrolled in the study after signing a written consent. The subjects received 5mgkg(-1) of cyclosporine orally and were genotyped for CYP3A5∗3 and CYP3A4∗18B using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)...
August 30, 2015: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/25932626/co-medication-of-statins-with-contraindicated-drugs
#16
Bo Ram Yang, Jong-Mi Seong, Nam-Kyong Choi, Ju-Young Shin, Joongyub Lee, Ye-Jee Kim, Mi-Sook Kim, Soyoung Park, Hong Ji Song, Byung-Joo Park
BACKGROUND: The concomitant use of cytochrome P450 3A4 (CYP3A4) metabolized statins (simvastatin, lovastatin, and atorvastatin) with CYP3A4 inhibitors has been shown to increase the rate of adverse events. OBJECTIVE: This study was performed to describe the co-medication prevalence of CYP3A4-metabolized statins with contraindicated drugs. METHODS: The patients aged 40 or older receiving CYP3A4-metabolized statin prescriptions in 2009 were identified using the national patient sample from a Korea Health Insurance Review and Assessment Service database...
2015: PloS One
https://www.readbyqxmd.com/read/25883814/severe-rhabdomyolysis-associated-with-simvastatin-and-role-of-ciprofloxacin-and-amlodipine-coadministration
#17
Nicolas De Schryver, Xavier Wittebole, Peter Van den Bergh, Vincent Haufroid, Eric Goffin, Philippe Hantson
Simvastatin is among the most commonly used prescription medications for cholesterol reduction and the most common statin-related adverse drug reaction is skeletal muscle toxicity. Multiple factors have been shown to influence simvastatin-induced myopathy. In addition to age, gender, ethnicity, genetic predisposition, and dose, drug-drug interactions play a major role. This is particularly true for drugs that are extensively metabolized by cytochrome P450 (CYP)3A4. We describe a particularly severe case of rhabdomyolysis after the introduction of ciprofloxacin, a weak CYP3A4 inhibitor, in a patient who previously tolerated the simvastatin-amlodipine combination...
2015: Case Reports in Nephrology
https://www.readbyqxmd.com/read/25807840/gender-specific-implications-for-pharmacology-in-childbearing-age-and-in-postmenopausal-women
#18
REVIEW
Joanna Bartkowiak-Wieczorek, Hubert Wolski, Anna Bogacz, Radosław Kujawski, Marcin Ożarowski, Marian Majchrzycki, Agnieszka Seremak-Mrozikiewicz
Women have three very important physiological functions that are not observed in men--menstruation, pregnancy and lactation. Each of these mechanisms influences pharmacokinetics and pharmacodynamics of many drugs. Individualization of pharmacotherapy is a major challenge of modern medicine. The differences in response to drug are responsible for the effectiveness of pharmacological treatment and the occurrence and severity of toxic effects and side effects. Therapeutic decision should be based not only on account of the dose-effect, but the consideration of gender, genetic and environmental differences affecting the final therapeutic effect...
February 2015: Ginekologia Polska
https://www.readbyqxmd.com/read/25794200/the-impact-of-genetic-variation-on-sensitivity-to-opioid-analgesics-in-patients-with-postoperative-pain-a-systematic-review-and-meta-analysis
#19
REVIEW
Zhen-Yu Ren, Xiao-Qing Xu, Yan-Ping Bao, Jie He, Le Shi, Jia-Hui Deng, Xue-Jiao Gao, Hui-Lin Tang, Yu-Mei Wang, Lin Lu
BACKGROUND: Individual response to opioid analgesics varies among patients. OBJECTIVE: This study sought to clarify the impact of distinct genetic variations on pain, opioid consumption, and opioid side effects in patients with postoperative pain. STUDY DESIGN: A systematic review and meta-analysis of associations between genetic single-nucleotide polymorphisms (SNPs) and opioids used for acute postoperative pain. SETTING: This meta-analysis examined all studies involving an association between genetic polymorphisms and the analgesic efficacy or clinical outcome of opioid analgesics for postoperative pain...
March 2015: Pain Physician
https://www.readbyqxmd.com/read/25266680/in-interaction-with-gender-a-common-cyp3a4-polymorphism-may-influence-the-survival-rate-of-chemotherapy-for-childhood-acute-lymphoblastic-leukemia
#20
A Gézsi, O Lautner-Csorba, D J Erdélyi, G Hullám, P Antal, Á F Semsei, N Kutszegi, M Hegyi, K Csordás, G Kovács, C Szalai
CYP3A4 has an important role in the metabolisms of many drugs used in acute lymphoblastic leukemia (ALL) therapy; still, there are practically no publications about the role of CYP3A4 polymorphisms in ALL pharmacogenomics. We genotyped eight common single-nucleotide polymorphisms (SNPs) in the CYP3A4 and CYP3A5 genes in 511 children with ALL and investigated whether they influenced the survival of the patients. We involved additional 127 SNPs in 34 candidate genes and searched for interactions with respect to the survival rates...
June 2015: Pharmacogenomics Journal
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