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Drug Metabolism and Personalized Therapy

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https://www.readbyqxmd.com/read/28315856/an-update-on-hla-alleles-associated-with-adverse-drug-reactions
#1
Ingrid Fricke-Galindo, Adrián LLerena, Marisol López-López
Adverse drug reactions (ADRs) are considered as an important cause of morbidity and mortality. The hypersensitivity reactions are immune-mediated ADRs, which are dose-independent, unpredictable and have been associated with several HLA alleles. The present review aimed to describe HLA alleles that have been associated with different ADRs in populations worldwide, the recommendations of regulatory agencies and pharmacoeconomic information and databases for the study of HLA alleles in pharmacogenetics. A systematic search was performed in June 2016 of articles relevant to this issue in indexed journals and in scientific databases (PubMed and PharmGKB)...
March 18, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28272018/genetic-polymorphisms-of-cytochrome-p450-enzymes-cyp2c9-cyp2c19-cyp2d6-cyp3a4-and-cyp3a5-in-the-croatian-population
#2
Lana Ganoci, Tamara Božina, Nikica Mirošević Skvrce, Mila Lovrić, Petar Mas, Nada Božina
BACKGROUND: Data on the frequency of pharmacogenetic polymorphisms in the Croatian population are limited. We determined and analyzed frequencies for the most important CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 genetic variants in the Croatian population. METHODS: 2637 subjects were included. Genotyping was performed by real-time polymerase chain reaction (PCR) using TaqMan® DME or TaqMan® SNP Genotyping Assays, and by PCR, and PCR-RFLP analysis. RESULTS: For CYP2C9, allele frequencies of *2 and *3 variant were 14...
March 1, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28259867/review-of-pharmacogenetics-studies-of-l-asparaginase-hypersensitivity-in-acute-lymphoblastic-leukemia-points-to-variants-in-the-gria1-gene
#3
Maria Lopez-Santillan, Leire Iparraguirre, Idoia Martin-Guerrero, Angela Gutierrez-Camino, Africa Garcia-Orad
Acute lymphoblastic leukemia (ALL) is a major pediatric cancer in developed countries. Although treatment outcome has improved owing to advances in chemotherapy, there is still a group of patients who experience severe adverse events. L-Asparaginase is an effective antineoplastic agent used in chemotherapy of ALL. Despite its indisputable indication, hypersensitivity reactions are common. In those cases, discontinuation of treatment is usually needed and anti-asparaginase antibody production may also attenuate asparaginase activity, compromising its antileukemic effect...
March 1, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28259866/verification-of-propofol-sulfate-as-a-further-human-propofol-metabolite-using-lc-esi-qqq-ms-and-lc-esi-qtof-ms-analysis
#4
Alexandra Maas, Christoph Maier, Beate Michel-Lauter, Sebastian Broecker, Burkhard Madea, Cornelius Hess
BACKGROUND: Propofol (2,6-diisopropylphenol) is a water-insoluble, intravenous anesthetic that is widely used for the induction and maintenance of anesthesia as well as for endoscopic and pediatric sedation. After admission, propofol undergoes extensive hepatic and extrahepatic metabolism, including direct conjugation to propofol glucuronide and hydroxylation to 2,6-diisopropyl-1,4-quinol. The latter substance subsequently undergoes phase II metabolism, resulting in the formation of further metabolites (1quinolglucuronide, 4quinolglucuronide and 4quinol-sulfate)...
March 1, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28253196/cytotoxicity-and-cytochrome-p450-inhibitory-activities-of-clinacanthus-nutans
#5
Suk Yen Quah, Jin Han Chin, Gabriel Akyirem Akowuah, Shaik Ibrahim Khalivulla, Siew Wei Yeong, Mandumpal Chacko Sabu
BACKGROUND: Clinacanthus nutans Lindau (family: Acanthaceae), also known as "Sabah Snake Grass" or "Belalai Gajah" in Malaysia, has been widely used by Malaysians due to its anticancer property. However, the anticancer activity of C. nutans leaves extract and its safe use need to be further investigated. The objectives of the present study were to evaluate the cytotoxic effects of methanol leaves extract of C. nutans in various human cancer cell lines and to evaluate the in vitro effect of C...
March 1, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28245187/influence-of-genetic-polymorphisms-of-cyp3a5-and-abcb1-on-sirolimus-pharmacokinetics-patient-and-graft-survival-and-other-clinical-outcomes-in-renal-transplant
#6
Consuelo Rodríguez-Jiménez, Mar García-Saiz, Lourdes Pérez-Tamajón, Eduardo Salido, Armando Torres
BACKGROUND: In transplant patients receiving de novo anticalcineurin-free sirolimus (SRL)-based immunosuppression, we determined the influence of cytochrome P450 3A5 (CYP3A5) and ATP-binding cassette, sub-family B (MDR/TAP), member (ABCB1) genotypes on SRL blood levels and medium-term relevant clinical outcomes, in order to improve effectiveness of immunosuppression strategies when anti-mammalian target of rapamycin (anti-mTOR) inhibitor is indicated for clinical reasons. METHODS: Forty-eight renal transplant recipients (suffered 48% diabetes mellitus, 91% hypertension, and 47% dyslipidemia) were genotyped for CYP3A5 (6986A>G) and ABCB1 (3435C>T) polymorphisms by polymerase chain reaction-restriction fragment length polymorphism...
March 1, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28231062/relationship-between-metabolic-phenotypes-and-genotypes-of-cyp1a2-and-cyp2a6-in-the-nigerian-population
#7
Ayorinde Adehin, Oluseye O Bolaji, Simran Maggo, Martin A Kennedy
BACKGROUND: CYP1A2 and CYP2A6 are polymorphic drug-metabolising enzymes that are also implicated in the activation of procarcinogens in humans. Some of their alleles and haplotypes, often varied in prevalence across populations, are thought to influence activity despite the known contribution of environmental factors. This study assessed the potential influence of some genetic variants of CYP1A2 and CYP2A6 on metabolic phenotypes in Nigerians. METHODS: Genomic DNA was extracted from blood samples of 100 healthy, unrelated subjects for whom CYP1A2 and CYP2A6 phenotypes had previously been determined, alongside an additional 80 other individuals for whom phenotype data were unavailable...
March 1, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28231061/role-of-treatment-modifying-mthfr677c-t-and-1298a-c-polymorphisms-in-metformin-treated-puerto-rican-patients-with-type-2-diabetes-mellitus-and-peripheral-neuropathy
#8
Francisco J Jiménez-Ramírez, Liza M Castro, Clarymar Ortiz, Jennifer Concepción, Jessicca Y Renta, Raúl H Morales-Borges, Jorge R Miranda-Massari, Jorge Duconge
BACKGROUND: The study was conducted to investigate potential association between MTHFR genotypes and diabetic peripheral neuropathy (DPN) in Puerto Ricans with type-2 diabetes mellitus (T2DM) treated with metformin. The prevalence of major MTHFR polymorphisms in this cohort was also ascertained. METHODS: DNAs from 89 metformin-treated patients with T2DM and DPN were genotyped using the PCR-based RFLP assay for MTHFR677C>T and 1298A>C polymorphisms. Frequency distributions of these variants in the study cohort were compared to those reported for three reference populations (HapMap project) and controls (400 newborn specimens)...
March 1, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28170339/genotyping-cyp2d6-by-three-different-methods-advantages-and-disadvantages
#9
Carolina Ribeiro, Patrícia Martins, Manuela Grazina
BACKGROUND: CYP2D6 belongs to P450 superfamily, and is responsible for the metabolism of 25% of the drugs used clinically. Genetic variability of CYP2D6 affects individual drug or toxic response leading to differences in the drug outcome or toxicity mediating adverse drug effects. The different variant alleles are associated with increased, decreased, or abolished enzyme hydroxylation functions. The CYP2D6*10 (rs1065852, c.100C>T) allele is associated with reduced function and is one of the most studied alleles...
March 1, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27889704/pharmacogenetic-studies-a-tool-to-improve-antidepressant-therapy
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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