scholarly journals ANALISIS POLIMORFISME CYP2D6*4 DAN CYP2D6*10 SEBAGAI METABOLIZER PRIMAKUIN DI RSUD JAYAPURA PAPUA INDONESIA

2021 ◽  
pp. 168-181
Author(s):  
Octavia Permata Sari
Keyword(s):  
Plasmodium Falciparum ◽  
Poor Metabolizer ◽  
Extensive Metabolizer ◽  
Pcr Rflp

Primakuin adalah antimalaria yang digunakan untuk mengeliminasi stadium gametosit Plasmodium falciparum dan stadium hipnozoit dari P. vivax. Efektivitas primakuin dipengaruhi oleh kemampuan individu dalam memetabolisme obat. Metabolisme primakuin utama diperankan melalui jalur enzim sitokrom P 450 2D6. Polimorfisme gen pengkode enzim tersebut, yakni gen CYP2D6 berdampak pada perubahan dalam kemampuan memetabolisme obat. Tujuan penelitian ini adalah untuk mengetahui distribusi genotipe dan frekuensi alotipe dari CYP2D6*4(G/A) dan CYP2D6*10(C/T). Metode yang digunakan untuk menilai polimorfisme pada penelitian ini adalah PCR-RFLP dengan desain penelitian deskriptif observasional. Hasil penelitian menunjukkan bahwa alel CYP2D6*4 yang dapat bermanifestasi sebagai poor metabolizer tidak ditemukan pada sampel penelitian. Frekuensi alel CYP2D6*10 yang dapat bermanifestasi sebagai intermediete metabolizer adalah 10%. Genotipe homozigot mutan CYP2D6*4 dan CYP2D6*10 tidak ditemukan pada penelitian ini. 100% sampel penelitian ini memiliki kemampuan metabolisme yang baik (extensive metabolizer) terhadap primakuin.

scholarly journals Increased Prevalence of Mutant Allele Pfdhps 437G and Pfdhfr Triple Mutation in Plasmodium falciparum Isolates from a Rural Area of Gabon, Three Years after the Change of Malaria Treatment Policy

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Jacques-Mari Ndong Ngomo ◽  
Denise Patricia Mawili-Mboumba ◽  
Noé Patrick M’Bondoukwe ◽  
Rosalie Nikiéma Ndong Ella ◽  
Marielle Karine Bouyou Akotet
Keyword(s):  
Plasmodium Falciparum ◽  
Dihydrofolate Reductase ◽  
Mutant Allele ◽  
Continuous Monitoring ◽  
Intermittent Preventive Treatment ◽  
Point Mutations ◽  
Preventive Treatment ◽  
Malaria Treatment ◽  
Pcr Rflp ◽  
Elevated Frequency

In Gabon, sulfadoxine-pyrimethamine (SP) is recommended for intermittent preventive treatment during pregnancy (IPTp-SP) and for uncomplicated malaria treatment through ACTs drug. P. falciparum strains resistant to SP are frequent in areas where this drug is highly used and is associated with the occurrence of mutations on Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pfdhps) genes. The aim of the study was to compare the proportion of mutations on Pfdhfr and Pfdhps genes in isolates collected at Oyem in northern Gabon, in 2005 at the time of IPTp-SP introduction and three years later. Point mutations were analyzed by nested PCR-RFLP method. Among 91 isolates, more than 90% carried Pfdhfr 108N and Pfdhfr 59R alleles. Frequencies of Pfdhfr 51I (98%) and Pfdhps 437G (67.7%) mutant alleles were higher in 2008. Mutations at codons 164, 540, and 581 were not detected. The proportion of the triple Pfdhfr mutation and quadruple mutation including A437G was high: 91.9% in 2008 and 64.8% in 2008, respectively. The present study highlights an elevated frequency of Pfdhfr and Pfdhps mutant alleles, although quintuple mutations were not found in north Gabon. These data suggest the need of a continuous monitoring of SP resistance in Gabon.

Genetically Determined Polymorphisms in Drug Metabolism

1992 ◽  
Vol 5 (6) ◽  
pp. 317-336
Author(s):  
Y.W. Francis Lam ◽  
Milton V. Marshall
Keyword(s):  
Drug Metabolism ◽  
Metabolic Pathway ◽  
Drug Response ◽  
Adverse Reactions ◽  
Drug Disposition ◽  
Poor Metabolizer ◽  
Extensive Metabolizer ◽  
Different Types ◽  
Metabolizing Enzyme ◽  
Genetically Determined

Many factors can influence the metabolism and disposition of drugs. Genetically determined differences in an individual's capacity to metabolize drugs are known causes of interindividual and interethnic variabilities in drug disposition and response. In general, a poor metabolizer for a specific metabolic pathway would likely develop adverse effects, and an extensive metabolizer for the same metabolic pathway might have less than optimal response. Although there are different types of polymorphism in drug metabolism, polymorphisms in debrisoquine-type oxidation, S-mephenytoin oxidation, and N-acetylation have been the most extensively studied. This article will present the basic concepts of pharmacogenetics, review the major types of metabolic polymorphisms, outline ways to determine phenotyping and genotyping differences in metabolizing enzyme activities, and discuss how these differences relate to drug metabolism, response, and toxicity. When evaluating drug response and adverse reactions in individual patients, an awareness of genetic differences in metabolic capacities would help contribute to optimization in drug therapy.

scholarly journals Chloroquine Phosphate Metabolism and Gender-based Phenotypic Analysis in Healthy Subjects’ Urine Following Oral Administration

2020 ◽  
Author(s):  
Samuel J. Bunu ◽  
Edebi N. Vaikosen ◽  
Kosi W. Nnadozie
Keyword(s):  
Quality Of Life ◽  
Healthy Subjects ◽  
Virus Disease ◽  
Biological Fluids ◽  
Poor Metabolizer ◽  
Phenotypic Analysis ◽  
Extensive Metabolizer ◽  
Significant Difference ◽  
Intermediate Metabolizer

Background: Chloroquine, 4-N-(7-chloroquinolin-4-yl)-1-N,-N-diethylpentane-1,4-diamine has promising activity against corona virus disease 2019 (COVID-19) and as such, it is imperative to thoroughly understand and determine the rate at which individual body systems metabolizes the drug. Chloroquine a known antimalarial drug belongs to the chemical class of 4-aminoquinolines. Objectives: The study aimed to analyze Chloroquine and its metabolite in biological fluids of healthy subjects by simple thin layer chromatography (TLC), which is an efficient, and inexpensive method for quantifying Chloroquine and its metabolites. Methods: A total of 30 healthy volunteers participated in the study by ingesting 500 mg of chloroquine, and the results were compared with side effects experienced by these subjects. Two brands of Chloroquine phosphate were used for the analysis and the urine were collected pre and post-drug administration and the intensities of the spots observed were compared with the reference standard stock solution. The same or greater intensity of sample spot indicates poor metabolizer, less intensity when compared to the stock spot indicates intermediate metabolizer while a much lesser intensity indicates an extensive metabolizer. Results: There was a statistically significant difference between the brands of chloroquine used at P<0.05. 30% of the volunteers were assigned poor metabolizer phenotype, 50% were assigned extensive metabolizer phenotype, and 20% assigned Intermediate metabolizer phenotype based on the intensity of spots observed. The majority of the poor metabolizers were females while the majority of the extensive metabolizers were males. Conclusion: Gender differences plays a vital the role in metabolism, therefore outine implementation of phenotype determination before therapy will therefore greatly improve the goal of therapy and quality of life. implementation of phenotype determination before therapy will, therefore, greatly improve the goal of therapy and quality of life.

Effect of CYP2D6 genetic polymorphism on peak propafenone concentration: no significant effect of CYP2D6*10

2020 ◽  
Vol 21 (18) ◽  
pp. 1279-1288
Author(s):  
Kosuke Doki ◽  
Yuki Shirayama ◽  
Yukio Sekiguchi ◽  
Kazutaka Aonuma ◽  
Yukinao Kohda ◽  
...  
Keyword(s):  
Genetic Polymorphism ◽  
Enzymatic Activity ◽  
Clinical Implication ◽  
Japanese Patients ◽  
Antiarrhythmic Therapy ◽  
Metabolic Ratio ◽  
Serum Concentrations ◽  
Poor Metabolizer ◽  
Extensive Metabolizer ◽  
Intermediate Metabolizer

Aim: The study aims to investigate the clinical implication of nonfunctional poor metabolizer (PM) alleles and intermediate metabolizer (IM) alleles of CYP2D6, including the CYP2D6*10 allele which shows substrate-dependent decrease in enzymatic activity, in antiarrhythmic therapy using propafenone. Materials & methods: We examined serum propafenone concentrations and metabolic ratio, which was expressed as serum concentrations of propafenone to 5-hydroxypropafenone, in 66 Japanese patients with tachyarrhythmias. Results: The peak propafenone concentration and metabolic ratio in CYP2D6 PM allele carriers were higher than those in extensive metabolizer (EM)/EM, EM/IM and IM/IM genotype groups. Conclusion: Results suggest that CYP2D6 PM alleles affect peak propafenone concentration, but the CYP2D6 IM allele CYP2D6*10 has no clinical implication in propafenone dosing.

scholarly journals Influence of smoking and CYP2C19 genotypes on H. pylori eradication success

2006 ◽  
Vol 135 (1) ◽  
pp. 171-176 ◽  
Author(s):  
T. SUZUKI ◽  
K. MATSUO ◽  
A. SAWAKI ◽  
K. WAKAI ◽  
K. HIROSE ◽  
...  
Keyword(s):  
Risk Factor ◽  
Drug Therapy ◽  
Success Rate ◽  
Independent Risk Factor ◽  
Eradication Therapy ◽  
Poor Metabolizer ◽  
Extensive Metabolizer ◽  
Opposite Trend ◽  
Genotype Interaction ◽  
H Pylori

CYP2C19 polymorphisms and smoking influence the efficacy of H. pylori eradication therapy, but interaction between the two have hitherto not been examined. A total of 142 H. pylori-positive patients who received triple drug therapy with lansoprazole, amoxicillin and clarithromycin were categorized into three groups with regard to diplotypes of CYP2C19: homozygous extensive metabolizer (homEM), heterozygous EM (hetEM), and poor metabolizer (PM). The overall success rate was 61·3%. Smoking was an independent risk factor of eradication failure (OR 2·81, 95% CI 1·14–6·91), whereas CYP2C19 polymorphisms were less influential. Among non-smokers, the homEM and hetEM groups showed worse eradication rates (58·5 and 67·3%) relative to PM (76·2%) as expected; however, an opposite trend was observed among smokers (homEM 50·0%, hetEM 46·7%, PM 20·0%), indicating possible interactions with CYP2C19 polymorphisms. Smoking has a greater influence on H. pylori eradication than the CYP2C19 genotype. Interaction between smoking and CYP2C19 should be examined in the future.

scholarly journals Field-based evidence of fast and global increase of Plasmodium falciparum drug-resistance by DNA-microarrays and PCR/RFLP in Niger

2009 ◽  
Vol 8 (1) ◽  
Author(s):  
Maman Laminou Ibrahim ◽  
Nicolas Steenkeste ◽  
Nimol Khim ◽  
Hadiza Hassane Adam ◽  
Lassana Konaté ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Dna Microarrays ◽  
Pcr Rflp ◽  
Global Increase

scholarly journals COMPARISON OF PCR-RFLP AND GENESCAN–BASED GENOTYPING FOR ANALYZING INFECTION DYNAMICS OF PLASMODIUM FALCIPARUM

2006 ◽  
Vol 74 (6) ◽  
pp. 944-950 ◽  
Author(s):  
NICOLE FALK ◽  
SETH OWUSU-AGYEI ◽  
TOM SMITH ◽  
NICOLAS MAIRE ◽  
HANS-PETER BECK ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Infection Dynamics ◽  
Pcr Rflp

Multiplex PCR–RFLP methods for pfcrt, pfmdr1 and pfdhfr mutations in Plasmodium falciparum

2006 ◽  
Vol 20 (2) ◽  
pp. 100-104 ◽  
Author(s):  
Maria Isabel Veiga ◽  
Pedro Eduardo Ferreira ◽  
Anders Björkman ◽  
José Pedro Gil
Keyword(s):  
Plasmodium Falciparum ◽  
Multiplex Pcr ◽  
Pcr Rflp

scholarly journals CYP2C19 Genotyping May Provide a Better Treatment Strategy when Administering Escitalopram in Chinese Population

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinyi Huang ◽  
Chao Li ◽  
Chaopeng Li ◽  
Zhenyu Li ◽  
Xiaohui Li ◽  
...  
Keyword(s):  
Steady State ◽  
Caucasian Population ◽  
Individual Treatment ◽  
Steady State Concentration ◽  
Poor Metabolizer ◽  
Extensive Metabolizer ◽  
The Poor ◽  
State Concentration ◽  
Depression Disorder ◽  
Intermediate Metabolite

Depression disorder is one of the most serious mental illnesses in the world. Escitalopram is the essential first-line medication for depression disorder. It is the substrate of hepatic cytochrome P450 (CYP) enzyme CYP2C19 with high polymorphism. The effect of CYP2C19 on pharmacokinetics and pharmacodynamics on Caucasian population has been studied. The Clinical Pharmacogenetics Implementation Consortium Guideline provides dosing recommendations for escitalopram on CYP2C19 genotypes on the basis of the studies on Caucasian population. However, the gene frequency of the alleles of CYP2C19 showed racial differences between Chinese and Caucasian populations. Representatively, the frequency of the *2 and *3 allele, which were considered as poor metabolizer, has been shown to be three times higher in Chinese than in Caucasians. In addition, the environments might also lead to different degrees of impacts on genotypes. Therefore, the guidelines based on the Caucasians may not be applicable to the Chinese, which induced the establishment of a guideline in China. It is necessary to provide the evidence of individual treatment of escitalopram in Chinese by studying the effect of CYP2C19 genotypes on the pharmacokinetics parameters and steady-state concentration on Chinese. In this study, single-center, randomized, open-label, two-period, two-treatment crossover studies were performed. Ninety healthy Chinese subjects finished the trials, and they were included in the statistical analysis. The pharmacokinetics characteristics of different genotypes in Chinese were obtained. The results indicate that the poor metabolizer had higher exposure, and increased half-life than the extensive metabolizer and intermediate metabolite. The prediction of steady-state concentration based on the single dose trial on escitalopram shows that the poor metabolizer might have a higher steady-state concentration than the extensive metabolizer and intermediate metabolite in Chinese. The results indicate that the genetic testing before medication and the adjustment of escitalopram in the poor metabolizer should be considered in the clinical treatments in Chinese. The results provide the evidence of individual treatment of escitalopram in Chinese, which will be beneficial for the safer and more effective application of escitalopram in the Chinese population.Clinical Trial Registration: identifier ChiCTR1900027226.

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