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Drug Metabolism and Personalized Therapy

Henrik Berg Rasmussen, Majbritt Busk Madsen
The carboxylesterase 1 gene (CES1) encodes a hydrolase that metabolizes commonly used drugs. The CES1-related pseudogene, carboxylesterase 1 pseudogene 1 (CES1P1), has been implicated in gene exchange with CES1 and in the formation of hybrid genes including the carboxylesterase 1A2 gene (CES1A2). Hence, the CES1 region is complex. Using in silico PCR and alignment, we assessed the specificity of PCR-assisted procedures for genotyping CES1, CES1A2 and CES1P1 in studies identified in PubMed. We identified 33 such studies and excluded those that were not the first to use a procedure or lacked sequence information...
February 10, 2018: Drug Metabolism and Personalized Therapy
Baraa Alghalyini, Said El Shamieh, Ali Salami, Sophie Visvikis Siest, Hana M Fakhoury, Rajaa Fakhoury
Background Statin therapy used to lower cholesterol levels results in a substantial reduction in cardiovascular complications. Previous observations in different ethnic populations showed that rs2306283A>G, p.Asn130Asp and rs4149056T>C, p.Val174Ala in solute carrier organic anion transporter 1B1 (SLCO1B1) gene encoding the organic transporter protein may be responsible for statin uptake, thus explaining the majority of statin-associated symptoms. In addition to the genetic component, vitamin D (vit D) deficiency is common in Saudi Arabia and worldwide and may cause muscle dysfunction and ache...
February 8, 2018: Drug Metabolism and Personalized Therapy
Kirsten M Pondman, Ron H N van Schaik, Jan van der Weide
BACKGROUND: CYP2D6 is responsible for the metabolism of approximately 25% of all drugs. The expression of cytochrome P450 2D6 (CYP2D6) is influenced by a combination of factors including polymorphisms in the CYP2D6 gene. Analysis of the CYP2D6 genotype is used to personalize the medication to a patient's metabolism. Although many genotypes can be determined using standard genotype analysis, in some cases, an incomplete analysis is performed. The CYP2D6 genotype *1/*4 often occurs in combination with a multiplication of the CYP2D6 gene, and is reported as (*1/*4)xN...
February 8, 2018: Drug Metabolism and Personalized Therapy
Dagmar F Hernandez-Suarez, Hector Núñez-Medina, Stuart A Scott, Angel Lopez-Candales, Jose M Wiley, Mario J Garcia, Kyle Melin, Karid Nieves-Borrero, Christina Rodriguez-Ruiz, Lorraine Marshall, Jorge Duconge
BACKGROUND: Antiplatelet therapy with clopidogrel is recommended to reduce cardiovascular events in patients with peripheral artery disease (PAD); however, clopidogrel efficacy has not been adequately studied in this patient population. Therefore, we aimed to determine the effects of cilostazol therapy on platelet reactivity among PAD patients on clopidogrel. METHODS: We performed a cross-sectional pilot study of 46 Puerto Rican patients diagnosed with PAD. The cohort was divided based on use of clopidogrel and cilostazol (n=24) or clopidogrel alone (n=22)...
February 6, 2018: Drug Metabolism and Personalized Therapy
Ana M Peiró, César Margargit, Adrián LLerena
No abstract text is available yet for this article.
January 6, 2018: Drug Metabolism and Personalized Therapy
Reenu Anne Joy, Narendranath Vikkath, Prasanth S Ariyannur
Hyaluronan is a ubiquitous high-molecular weight polymer of repeated disaccharides of glucuronic acid and N-acetylglucosamine. It is a membrane-bound, viscous material extruded into the extracellular matrix after being synthesized in the cytoplasm by hyaluronan synthases complex and a regulated degradation by a group of enzymes called hyaluronidases. Hyaluronan has varied biological roles on many vital organismal functions, such as cellular and tissue development, migration and repair after injury or inflammation and cancer genesis...
March 28, 2018: Drug Metabolism and Personalized Therapy
Swarup A V Shah, Minal U Paradkar, Devendra C Desai, Tester F Ashavaid
BACKGROUND: Thiopurine methyltransferase (TPMT) gene variants have achieved limited success in predicting the outcome of thiopurine therapy, which shows wide inter-individual variations. The literature indicates a strong association between the NUDT15 gene variant and thiopurine-induced toxicity in Asian patients. The present study intends to explore the role of the NUDT15 variant (C415T) in Indian patients on thiopurine therapy. METHODS: NUDT15 and TPMT genotyping were performed using amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) and the restriction fragment length polymorphism (RFLP) technique...
March 28, 2018: Drug Metabolism and Personalized Therapy
Ursula Amstutz, Vid Mlakar, Patricia Huezo-Diaz Curtis, Caroline Samer, Pierre Baumann, Roland P Bühlmann, Peter Meier-Abt, Urs A Meyer, Ron H N van Schaik, Marc Ansari
No abstract text is available yet for this article.
December 20, 2017: Drug Metabolism and Personalized Therapy
Georgia Ragia, Ioanna-Maria Karantza, Eleni Kelli-Kota, Vana Kolovou, Genovefa Kolovou, Stavros Konstantinides, Efstratios Maltezos, Anna Tavridou, Dimitrios Tziakas, Anke H Maitland-van der Zee, Vangelis G Manolopoulos
BACKGROUND: We have earlier developed a pharmacogenomic algorithm for acenocoumarol dose prediction in Greek patients that included CYP2C9/VKORC1 genetic information. This study aims at analyzing the potential effect of CYP4F2, CYP2C19, and CYP1A2 gene polymorphisms on acenocoumarol dose requirements and at further improving the Greek-specific pharmacogenomic algorithm. METHODS: A total of 205 Greek patients taking acenocoumarol (140 who reached and 65 who did not reach stable dose), participants of acenocoumarol EU-PACT trial, were included in the study...
December 20, 2017: Drug Metabolism and Personalized Therapy
Carlos L Pérez, Maria T Donato, Ivones Hernández, Miriam T Paz Lopes, Evangelina Marrero, Jose A Herrera, Maria J Gómez-Lechón, Idania Rodeiro
BACKGROUND: The aqueous extract of the Allophylus cominia (L) Sw (Sapindaceae) leaves has shown anti-diabetic, anti-obesity and anti-inflammatory properties. In the Caribbean region, it is typically used for the treatment of type-2 diabetes. METHODS: Considering the herb-drug interaction, the aim of this study was to evaluate the potential effects of the A. cominia extract on the cytochrome P450 (CYP) (rat hepatocyte model) and P-glycoprotein (P-gp) (4T1 cell line) systems...
December 20, 2017: Drug Metabolism and Personalized Therapy
Ken-Ichi Umehara, Felix Huth, Helen Gu, Hilmar Schiller, Tycho Heimbach, Handan He
BACKGROUND: For estimation of fractions metabolized (fm) by different hepatic recombinant human CYP enzymes (rhCYP), calculation of inter-system extrapolation factors (ISEFs) has been proposed. METHODS: ISEF values for CYP1A2, CYP2C19 and CYP3A4/5 were measured. A CYP2C9 ISEF was taken from a previous report. Using a set of compounds, fractions metabolized by CYP enzymes (fm,CYP) values calculated with the ISEFs based on rhCYP data were compared with those from the chemical inhibition data...
December 20, 2017: Drug Metabolism and Personalized Therapy
Heike Jahnke
No abstract text is available yet for this article.
December 19, 2017: Drug Metabolism and Personalized Therapy
Carlos A Castro-Rojas, Antonio R Esparza-Mota, Francisco Hernandez-Cabrera, Viktor J Romero-Diaz, Juan F Gonzalez-Guerrero, Hector Maldonado-Garza, Irma S Garcia-Gonzalez, Sergio Buenaventura-Cisneros, Josefina Y Sanchez-Lopez, Rocio Ortiz-Lopez, Alberto Camacho-Morales, Oralia Barboza-Quintana, Augusto Rojas-Martinez
BACKGROUND: Fluoropyrimidines form the chemotherapy backbone of advanced and metastatic colorectal cancer (CRC). These drugs are frequently associated with toxicity events that result in dose adjustments and even suspension of the treatment. The thymidylate synthase (TYMS) gene is a potential marker of response and toxicity to fluoropyirimidines as this enzyme is the molecular target of these drugs. Our aim was to assess the association between variants of TYMS with response and toxicity to fluoropyrimidines in patients with CRC in independent retrospective and prospective studies...
December 19, 2017: Drug Metabolism and Personalized Therapy
Jaroslav A Hubacek, Vera Adamkova, Lukas Zlatohlavek, Lenka Steiner-Mrazova, Michal Vrablik
BACKGROUND: The gene COQ2, encoding 4-hydroxybenzoate-polyprenyltransferase (coenzyme Q2), belongs to the candidates potentially influencing statin treatment tolerability. This enzyme is involved in the biosynthesis of coenzyme Q10 (CoQ10), in which depletion induced by statin treatment is implicated in the development of statin-associated muscle symptoms (SAMS). Thus, polymorphisms in the COQ2 gene might explain susceptibility to SAMS. METHODS: Adult patients with SAMS (on low doses of atorvastatin and simvastatin)-induced myalgia/myopathy (n=278), patients on statins but without SAMS (n=293) and population (part of the post-MONICA [Multinational MONItoring of trends and determinants in CArdiovascular disease] study) controls (n=561) were genotyped (polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] assay) for rs6535454 and rs4693075 polymorphisms within the COQ2 gene loci...
December 19, 2017: Drug Metabolism and Personalized Therapy
Harminder Singh, Baltej Singh
BACKGROUND: The objective of this study was to evaluate the occurrence of drug-drug interactions (DDIs) in patients on cancer chemotherapy, with the identification of risk factors for these DDIs. METHODS: This was a cross-sectional, descriptive study carried out at the Department of Onco-Radiation at Guru Gobind Singh Medical College, Faridkot, Punjab. The DDIs were recorded with the help of a drug interaction/interplay information software. RESULTS: In total, 354 interactions were identified from 283 patient records...
November 14, 2017: Drug Metabolism and Personalized Therapy
Bardia Jamali, Behjat Sheikholeslami, Yalda Hosseinzadeh Ardakani, Hoda Lavasani, Mohammad-Reza Rouini
BACKGROUND: Tramadol is prone to be abused alone, or in combination with 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy). It was reported that 95% of people with a history of substance abuse in the United States used tramadol in 2004. According to the WHO report in 2016, there was a growing number of tramadol abusers alone or in combination with psychoactive substances such as MDMA in particular in some Middle East countries. Higher concentrations of tramadol in plasma may lead to adverse drug reactions or lethal intoxication...
September 26, 2017: Drug Metabolism and Personalized Therapy
Janthima Methaneethorn, Duangchit Panomvana, Thaveechai Vachirayonstien
BACKGROUND: Therapeutic drug monitoring is essential for both phenytoin and phenobarbital therapy given their narrow therapeutic indexes. Nevertheless, the measurement of either phenytoin or phenobarbital concentrations might not be available in some rural hospitals. Information assisting individualized phenytoin and phenobarbital combination therapy is important. This study's objective was to determine the relationship between the maximum rate of metabolism of phenytoin (Vmax) and phenobarbital clearance (CLPB), which can serve as a guide to individualized drug therapy...
September 26, 2017: Drug Metabolism and Personalized Therapy
Nancy Hakooz, Yazun Bashir Jarrar, Malik Zihlif, Amer Imraish, Saja Hamed, Tawfiq Arafat
BACKGROUND: Human response to the antidiabetic metformin is influenced by some factors, such as genetic variants in the SLC22A genes. This study aimed to determine the frequency of main SLC22A1 and SLC22A3 genetic variants and their influence on metformin pharmacokinetics among healthy unrelated Arab Jordanians. PATIENTS AND METHODS: The SLC22A1 and SLC22A3 genes were genotyped by DNA sequencing of exons 1, 3, 7, and 9 in the SLC22A1 gene and exons 6, 7, and 9 in the SLC22A3 gene...
September 26, 2017: Drug Metabolism and Personalized Therapy
Raúl H Morales-Borges
Methylenetetrahydrofolate reductase (MTHFR) mutations have been linked to many diseases. Evidence has been provided to prove that we need to perform pharmacogenetic studies regarding the prevalence of MTHFR mutations and diseases, risks, and the impact on folate requirement in general, but little has been published about Puerto Ricans. A multi center cross-sectional retrospective review study or a prospective pharmacogenetic study of valid genotypes and phenotypes of MTHFR mutations within the different populations of Puerto Ricans and Hispanics are recommended, because differences within them and within the general population are expected...
September 26, 2017: Drug Metabolism and Personalized Therapy
Henrik Berg Rasmussen, Majbritt Busk Madsen, Yassine Kamal Lyauk, Peter Riis Hansen, Timothy Hughes
The carboxylesterase 1 gene (CES1) encodes a hydrolase implicated in the metabolism of commonly used drugs. CES1A2, a hybrid of CES1 and a CES1-like pseudogene, has a promoter that is weak in most individuals. However, some individuals harbor a promoter haplotype of this gene with two overlapping Sp1 sites that confer significantly increased transcription potentially leading to rapid drug metabolism. This CES1A2 haplotype has previously been reported to be common among Asians. Using polymerase chain reaction followed by sequencing, the present study examined variation in the promoter and 5' untranslated region of CES1A2 in 120 Han Chinese and 120 Japanese people enrolled in the 1000 Genomes Project...
September 26, 2017: Drug Metabolism and Personalized Therapy
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