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Drug Metabolism and Personalized Therapy

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https://www.readbyqxmd.com/read/27889704/pharmacogenetic-studies-a-tool-to-improve-antidepressant-therapy
#1
Marta Ramos, Cecilia Berrogain, Julia Concha, Laura Lomba, Cristina Belén García, Mª Pilar Ribate
The World Health Organization (WHO) predicts that major depressive disorder (MDD) will be the second leading cause of death and disability by 2020. Nowadays, approximately 60-70% of patients with this disorder have shown the lack of effectiveness and tolerability of the therapy with antidepressants. The US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) are including pharmacogenetic information in the labeling of several antidepressants. The presence of this information represents the relevance of genetic polymorphisms in drug response...
December 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27889703/the-santorini-conferences-continue
#2
Sofia Siest
No abstract text is available yet for this article.
December 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27875319/enhanced-oral-bioavailability-of-metoprolol-with-gallic-acid-and-ellagic-acid-in-male-wistar-rats-involvement-of-cyp2d6-inhibition
#3
Bhargavi Latha Athukuri, Prasad Neerati
BACKGROUND: Cytochrome P450-2D6 (CYP2D6), a member of the CYP450 mixed function oxidase system, is an important CYP isoform with regard to herbal-drug interactions and is responsible for the metabolism of nearly 25% of drugs. Until now, studies on the effects of various phytochemicals on CYP2D6 activity in vivo have been very rare. Gallic acid and ellagic acid are natural polyphenols which are widely distributed in fruits and medicinal plants. In the present study, the effects of gallic acid and ellagic acid pretreatment on intestinal transport and oral bioavailability of metoprolol were investigated...
December 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27875318/1846g-a-polymorphism-of-cyp2d6-gene-and-extrapyramidal-side-effects-during-antipsychotic-therapy-among-russians-and-tatars-a-pilot-study
#4
Dmitriy A Sychev, Irina S Burashnikova, Ruslan E Kazakov
BACKGROUND: Сytochrome P450 CYP2D6 activity affects antipsychotic therapy safety. 1846G>A (CYP2D6*4) polymorphism frequency varies among different ethnic groups. METHODS: We studied 1846G>A polymorphism in Tatar and Russian schizophrenic patients taking different antipsychotics and association of 1846G>A polymorphism and extrapyramidal disorders (EPD) frequency in schizophrenic patients on haloperidol monotherapy in daily doses up to 20 mg. RESULTS: Heterozygous 1846GA genotype frequency among Tatars was lower (23...
December 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27875317/cyp2d6-variability-in-populations-from-venezuela
#5
Nancy Moreno, Carlos Flores-Angulo, Cecilia Villegas, Yuselin Mora
CYP2D6 is an important cytochrome P450 enzyme that plays an important role in the metabolism of about 25% of currently prescribed drugs. The presence of polymorphisms in the CYP2D6 gene may modulate enzyme level and activity, thereby affecting individual responses to pharmacological treatments. The most prevalent diseases in the admixed population from Venezuela are cardiovascular and cancer, whereas viral, bacterial and parasitic diseases, particularly malaria, are prevalent in Amerindian populations; in the treatment of these diseases, several drugs that are metabolized by CYP2D6 are used...
December 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27849621/vancomycin-induced-thrombocytopenia-in-a-newborn
#6
Kunal Kalra, Hema Gupta Mittal, Arti Maria
Neonatal thrombocytopenia is common and is frequently seen in neonatal sepsis. Drug-induced thrombocytopenia is likely to be missed unless a high index of suspicion is present. Changing of antibiotics for assumed nonresolution of sepsis may lead to persistent thrombocytopenia in a neonate if drug-induced thrombocytopenia is missed. Vancomycin-induced neonatal thrombocytopenia is rarely described in scientific literature. We describe a newborn who was diagnosed with early onset sepsis and vancomycin-induced thrombocytopenia...
December 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27828777/slc22a2-mapping-genomic-variations-within-south-african-indigenous-and-admixed-populations
#7
Brendon Pearce, Clifford Jacobs, Nisreen Hoosain, Mongi Benjeddou
BACKGROUND: The SLC22A2 gene is a polyspecific transporter that mediates the electrogenic transport of small organic cations with different molecular structures. Furthermore, single-nucleotide polymorphisms (SNPs) of SLC22A2 are clinically significant because they can alter the transport of substrate drugs and may, thus, influence the efficacy and toxicity thereof. Additionally, further studies have reported that SLC22A2 is responsible for 80% of the total metformin clearance. Therefore, loss-of-function variants of SLC22A2 could affect the pharmacokinetic and pharmacodynamic characteristics of metformin...
December 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27740916/can-pharmacogenetics-help-patients-under-chronic-treatment-with-coumarin-anticoagulants
#8
Isabel López, Estela Sangüesa, Yves Vancraenendonck, Estefanía Zuriaga, María Pilar Ribate, Cristina Belén García
Vitamin K antagonists are highly effective antithrombotic drugs. However, appropriate dosing is difficult to establish owing to its narrow therapeutic window as well as widespread inter- and intra-individual variability in dosage. Compared with dosing solely based on clinical information, pharmacogenetics can help improve the therapy with coumarins by decreasing the time to reach a stable dose and reducing the risk of bleeding. Most of the studies about genotyping of patients using vitamin K antagonists have focused on predicting the stable dose...
December 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27718490/improvement-of-the-chemical-inhibition-phenotyping-assay-by-cross-reactivity-correction
#9
Nicholas M Njuguna, Ken-Ichi Umehara, Felix Huth, Hilmar Schiller, Kelly Chibale, Gian Camenisch
BACKGROUND: The fraction of an absorbed drug metabolized by the different hepatic cytochrome P450 (CYP) enzymes, relative to total hepatic CYP metabolism (fmCYP), can be estimated by measuring the inhibitory effects of presumably selective CYP inhibitors on the intrinsic metabolic clearance of a drug using human liver microsomes. However, the chemical inhibition data are often affected by cross-reactivities of the chemical inhibitors used in this assay. METHODS: To overcome this drawback, the cross-reactivities exhibited by six chemical inhibitors (furafylline, montelukast, sulfaphenazole, ticlopidine, quinidine and ketoconazole) were quantified using specific CYP enzyme marker reactions...
December 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27662649/the-impact-of-cyp4f2-abcb1-and-ggcx-polymorphisms-on-bleeding-episodes-associated-with-acenocoumarol-in-russian-patients-with-atrial-fibrillation
#10
Dmitriy Alexeyevich Sychev, Aleksandr Vladimirovich Rozhkov, Ruslan Evgenyevich Kazakov, Anna Viktorovna Ananichuk
BACKGROUND: Oral anticoagulants are commonly used to treat patients with thromboembolic pathology. Genetic variations could influence personal response to anticoagulant drugs. Acenocoumarol (AC) is a vitamin K antagonist used in anticoagulant therapy and as a prophylaxis measure in Europe. In this study, we assessed the effect of CYP4F2 rs2108622, ABCB1, and GGCX polymorphisms on the safety profile and regime dosing of AC in patients with nonvalvular atrial fibrillation. METHODS: Fifty patients aged 40-70 years were included...
September 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27662648/pharmacogenomics-in-pain-treatment
#11
Ana M Peiró, Beatriz Planelles, Gabriella Juhasz, György Bagdy, Frédéric Libert, Alain Eschalier, Jérôme Busserolles, Beata Sperlagh, Adrián Llerena
The experience of chronic pain is one of the commonest reasons for seeking medical attention, being a major issue in clinical practice. While pain is a universal experience, only a small proportion of people who felt pain develop pain syndromes. In addition, painkillers are associated with wide inter-individual variability in the analgesic response. This may be partly explained by the presence of single nucleotide polymorphisms in genes encoding molecular entities involved in pharmacodynamics and pharmacokinetics...
September 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27522101/altered-pharmacokinetics-of-rosiglitazone-in-a-mouse-model-of-non-alcoholic-fatty-liver-disease
#12
Nagaraj M Kulkarni, Sandeep Malampati, Mahamad Yunnus A Mahat, S Chandrasekaran, J Raghul, Ansar Ali Khan, Uma Maheswari Krishnan, Shridhar Narayanan
BACKGROUND: Severe forms of non-alcoholic fatty liver disease (NAFLD) adversely affect the liver physiology and hence the pharmacokinetics of drugs. Here, we investigated the effect of NAFLD on the pharmacokinetics of rosiglitazone, an insulin sensitizer used in the treatment of type 2 diabetes. METHODS: Male C57BL/6 mice were divided into two groups. The first group (n=14) was fed with normal chow feed and the second group (n=14) was fed with 60% high-fat diet (HFD) and 40% high fructose liquid (HFL) for 60 days to induce NAFLD...
September 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27474842/pharmacogenetic-approach-to-losartan-in-marfan-patients-a-starting-point-to-improve-dosing-regimen
#13
Felicia Stefania Falvella, Susan Marelli, Stefania Cheli, Stefano Montanelli, Federico Viecca, Lucia Salvi, Alfio Ferrara, Emilio Clementi, Giuliana Trifirò, Alessandro Pini
BACKGROUND: Losartan is under evaluation for managing Marfan patients with aortic root dilatation. Cytochrome P450 (CYP) enzymes convert losartan to E3174 active metabolite. The aim of this study is to describe the distribution of CYP2C9*2, CYP2C9*3, CYP3A4*22 and CYP3A5*3 defective alleles, according to losartan tolerance in paediatric Marfan patients. METHODS: We genotyped 53 paediatric Marfan patients treated with losartan. The rate of aortic root dilatation was evaluated using the delta z-score variation...
September 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27447243/association-study-of-drd2-a2-a1-drd3-ser9gly-d%C3%AE-h-1021c-t-oprm1-a118g-and-grik1-rs2832407c-a-polymorphisms-with-alcohol-dependence
#14
Georgia Ragia, Ivan Veresies, Louiza Veresie, Kyriakos Veresies, Vangelis G Manolopoulos
BACKGROUND: The reinforcing effects of alcohol are mediated through complex interactions between multiple neurochemical systems. Genes of dopaminergic (DRD2, DRD3 and DβH), opioid (OPRM1) and glutaminergic (GRIK1) systems mediate the dependent behavior via different mechanisms; however, they all target the serotonergic and dopaminergic pathways in the ventral tegmental area. METHODS: In the present study, DRD2 A2/A1, DRD3 Ser9Gly, DβH -1021C>T, OPRM1 A118G and GRIK1 rs2832407C>A polymorphisms and their interactions were analyzed in 72 alcohol-dependent patients and 74 controls of Greek-Cypriot origin, using the PCR-RFLP method...
September 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27404905/medication-therapy-management-mtm-an-innovative-approach-to-improve-medication-adherence-in-diabetics
#15
Athira Bindu Murali, Belsy Boban, Aswathy Karoor Shanmughan, Karthikeyan Marimuthu, Aravind Ramakrishnan Sreelatha, Augustine Xavier
BACKGROUND: Medication therapy management (MTM) is a pharmacist-led professional service, one of the main aims of which is to improve patient medication adherence. Ensuring adequate adherence to the prescribed therapeutic regimen is one of the major challenges in attaining the desired therapeutic goals in diabetics. The objective of this study was to implement MTM in diabetic patients and to identify its effectiveness in improving patient medication adherence. METHODS: A prospective interventional study was carried out within a 1-year period in KIMS-Al-Shifa Hospital, which is a tertiary care referral hospital in Malabar region of Kerala, including inpatients with type 2 diabetes mellitus in the general medicine department of the hospital...
September 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27269898/the-integration-and-interpretation-of-pharmacogenomics-a-comparative-study-between-the-united-states-of-america-and-europe-towards-better-health-care
#16
Mark J Bartlett, Elizabeth A Shephard
The study of pharmacogenomics has, by harnessing sequence information from human genomes, the potential to lead to novel approaches in drug discovery, an individualized application of drug therapy, and new insights into disease prevention. For this potential to be realized results need to be interpreted to the prescriber into a format which dictates an action. This mini review briefly describes the history, the regulatory environment, opinions towards, and implementation, integration and interpretation of pharmacogenomics in the United States of America and Europe...
June 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27226103/lack-of-genomic-diversity-in-the-slc47a1-gene-within-the-indigenous-xhosa-population
#17
Clifford Jacobs, Brendon Pearce, Nisreen Hoosain, Mongi Benjeddou
BACKGROUND: Multidrug and toxin extrusion 1 (MATE1) is an organic cation/H+ exchanger, localized in the apical membrane of proximal renal tubules, which mediates the cellular elimination of organic cations into the renal lumen. These organic cations include clinically important drugs such as metformin, oxaliplatin and cimetidine. Moreover, genetic polymorphisms of SLC47A1, the pharmacogenetically relevant gene encoding human MATE1, have been implicated in reduced transport or accumulation to cytotoxic levels of these drugs in vitro...
June 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27166727/altered-pharmacokinetics-and-pharmacodynamics-of-repaglinide-by-ritonavir-in-rats-with-healthy-diabetic-and-impaired-hepatic-function
#18
Thirumaleswara Goud, Srinivas Maddi, Devanna Nayakanti, Rajendra Prasad Thatipamula
BACKGROUND: Ritonavir is an antiretroviral drug to treat HIV AIDS and inhibits cytochrome P450 3A4. To treat diabetes mellitus in HIV, repaglinide is coadministered with ritonavir in the clinic. Multiple cytochrome P450 (CYP) isoforms are involved in the metabolism of repaglinide like CYP2C8 and CYP 3A4. In order to predict and understand drug-drug interactions of these two drugs, the pharmacokinetics and pharmacodynamics (PK/PD) of repaglinide and ritonavir were studied in normal, diabetic and hepatic impaired rats...
June 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/26974145/predictive-biomarkers-candidates-for-patients-with-metastatic-colorectal-cancer-treated-with-bevacizumab-containing-regimen
#19
Nicolás González-Vacarezza, Isabel Alonso, Gustavo Arroyo, Jorge Martínez, Fernando De Andrés, Adrián LLerena, Francisco Estévez-Carrizo
Bevacizumab was the first molecular-targeted antiangiogenic therapy approved for the treatment of metastatic colorectal cancer. Until now, there are no predictive biomarkers available to decide the prescription of bevacizumab in patients with colorectal cancer. The purposes of this review were to provide a critical appraisal of the evidence and to identify possible predictive genetic biomarkers. A literature search was performed to identify studies that determine different levels of treatment response between patients stratified according to defined biomarkers...
June 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/26959552/assessment-of-cytochrome-p450-inhibition-and-induction-potential-of-lupeol-and-betulin-in-rat-liver-microsomes
#20
Madhav Seervi, Shweta Lotankar, Shrikant Barbar, Sadhana Sathaye
BACKGROUND: Lupeol and betulin are triterpenoids that are majorly found in dietary substances. The aim of present study was to investigate the inhibition and induction potential of lupeol and betulin on cytochrome P450 (CYP)1A2, CYP2C11, CYP2D6 and CYP3A2 activities in rat liver microsomes. METHODS: The inhibition and induction studies were conducted using ethoxy resorufin-O-deethylase (CYP1A2), tolbutamide hydroxylase (CYP2C9), and midazolam hydroxylase (CYP3A4) activity assays...
June 1, 2016: Drug Metabolism and Personalized Therapy
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