A5026578786- Drug Transport and Resistance Mechanisms
- Pharmacological Effects and Toxicity Studies
- Pharmacogenetics and Drug Metabolism
- Amino Acid Enzymes and Metabolism
- Metabolism and Genetic Disorders
- Hormonal Regulation and Hypertension
- Gastroesophageal reflux and treatments
- Adenosine and Purinergic Signaling
- Cannabis and Cannabinoid Research
- Antibiotics Pharmacokinetics and Efficacy
- Drug Solubulity and Delivery Systems
- Sepsis Diagnosis and Treatment
- Advanced Drug Delivery Systems
- Ion Transport and Channel Regulation
- Epigenetics and DNA Methylation
- Analytical Methods in Pharmaceuticals
- Gastrointestinal motility and disorders
- Folate and B Vitamins Research
- Epilepsy research and treatment
- Receptor Mechanisms and Signaling
- Immune Response and Inflammation
- Coffee research and impacts
- Genetic Associations and Epidemiology
- Biochemical and Molecular Research
- Heart Failure Treatment and Management
Universitätsmedizin Greifswald
2018-2025
University of Göttingen
2012-2021
Universitätsmedizin Göttingen
2012-2021
Universität Greifswald
2018-2021
University of Vienna
2020
University of Würzburg
2018
Johannes Gutenberg University Mainz
2005-2010
University Medical Center
2010
Saarland University
2005
University of Oslo
2005
A significant number of patients treated with anthracyclines develop cardiotoxicity (anthracycline-induced [ACT]), mainly presenting as arrhythmias (acute ACT) or congestive heart failure (chronic ACT). There are no data on pharmacogenomic predictors ACT.We genotyped participants the German non-Hodgkin lymphoma study (NHL-B) who were followed up for development a median >3 years. Single-nucleotide polymorphisms (SNPs) selected from 82 genes conceivable relevance to ACT. Of 1697 patients, 55...
Organic cation transporters (OCTs) can mediate metformin transmembrane transport. We explored pharmacokinetics in relation to genetic variations OCT1, OCT2, OCT3, OCTN1, and MATE1 103 healthy male Caucasians. Renal clearance varied 3.8-fold was significantly dependent on creatinine (r2 = 0.42, P < 0.0001), age 0.09, 0.002), OCT1 polymorphisms. Carriers of zero, one, two low-activity alleles (Arg61Cys, Gly401Ser, 420del, or Gly465Arg) had mean renal clearances 30.6, 33.1, 37.1 l/h,...
We investigated whether morphine and its pro-drug codeine are substrates of the highly genetically polymorphic organic cation transporter OCT1 polymorphisms may affect pharmacokinetics in humans. Morphine showed low transporter-independent membrane permeability (0.5 × 10⁻⁶ cm/s). uptake was increased up to 4-fold HEK293 cells overexpressing human OCT1. The increase concentration-dependent followed Michaelis-Menten kinetics (KM = 3.4 μM, VMAX 27 pmol/min/mg protein). OCT1-mediated abolished...
We investigated whether tramadol or its active metabolite, O-desmethyltramadol, are substrates of the organic cation transporter OCT1 and polymorphisms in affect O-desmethyltramadol pharmacokinetics. Tramadol showed high permeability through parallel artificial membrane assays (PAMPAs). uptake HEK293 cells did not change after overexpression, concentrations plasma healthy volunteers were independent their genotypes. In contrast, low permeability, overexpression increased 2.4-fold. This...
Introduction In the treatment of heart failure and hypertension with metoprolol, ultrarapid metabolizers (UMs) may not achieve optimal target concentrations recommended doses. We compared metoprolol pharmacokinetics effects in UMs extensive (EMs) poor (PM) as an additional reference group. Methods After a single dose 100 mg pharmacokinetics, resting exercise rate, blood pressure were analyzed relation to CYP2D6 genotypes. included 12 UMs, 13 EMs, 4 PMs (healthy volunteers). genotyping...
Gong, Li; Stamer, Ulrike M.; Tzvetkov, Mladen V.; Altman, Russ B.; Klein, Teri E. Author Information
The low bioavailability of the anti‐migraine drug sumatriptan is partially caused by first‐pass hepatic metabolism. In this study, we analyzed impact organic cation transporter OCT1 on cellular uptake, and polymorphisms pharmacokinetics. transported with high capacity uptake into human hepatocytes was strongly inhibited inhibitor MPP + . Sumatriptan not affected Met420del polymorphism, but reduced Arg61Cys Gly401Ser, completely abolished Gly465Arg Cys88Arg. Plasma concentrations in humans...
Genetic variation in the pharmacokinetics of metoprolol and torsemide due to polymorphisms CYP2D6 , CYP2C9 OATP1B1 has been extensively studied. However, it is still unknown how much these two clinically important drugs total genetic factors. Metoprolol were intravenously administered 44 monozygotic 14 dizygotic twin pairs. area under curve (AUC) varied 4.7‐fold AUC 3.5‐fold. A very high fraction variations, 91% 86% torsemide, found be additive effects. known variants CYP2D6, ‐2C9, explained...
Fenoterol is a widely used anti-asthmatic and tocolytic agent, but high plasma concentrations of fenoterol may lead to severe even fatal adverse reactions. We studied whether heritable deficiency the liver organic cation transporter 1 (OCT1), trait observed in 3% Europeans white Americans, affects toxicity. OCT1 transported with affinity, inhibition human hepatocytes reduced uptake threefold. After administration 180 µg 39 healthy individuals, OCT1-deficient individuals (zero active alleles;...
The impact of the CYP2C9 polymorphism on pharmacokinetics orally administered Δ9-tetrahydrocannabinol (THC) was studied in 43 healthy volunteers. THC did not differ by CYP2C9*2 allele status. However, median area under curve threefold higher and that 11-nor-9-carboxy-9-tetrahydrocannabinol 70% lower CYP2C9*3/*3 homozygotes than CYP2C9*1/*1 homozygotes. CYP2C9*3 carriers also showed a trend toward increased sedation following administration THC. Therefore, variant may influence both...
Objective Genetic variability within the serotoninergic system may predict response to antidepressant drugs. Several polymorphisms in gene coding for brain-specific tryptophan hydroxylase (TPH2) have been associated with susceptibility psychiatric diseases. In this study, we analyzed correlation between TPH2 and Methods The study included 182 patients who received drug treatment major depression. To assess gene, four single nucleotide (SNPs) tagging common haplotypes six SNPs medically...
Ranitidine (Zantac®) is a H2-receptor antagonist commonly used for the treatment of acid-related gastrointestinal diseases. was reported to be substrate organic cation transporters OCT1 and OCT2. The hepatic transporter highly genetically variable. Twelve major alleles confer partial or complete loss activity. effects these polymorphisms are substrate-specific therefore difficult predict. renal OCT2 has common polymorphism, Ala270Ser, which affect activity.In this study we analyzed genetic...
Abstract The organic cation transporter OCT1 (SLC22A1) mediates uptake and metabolism of the active tramadol metabolite (+) O -desmethyltramadol in liver. In this study, influence genetic polymorphisms on pharmacokinetics analgesic efficacy patients recovering from surgery was analyzed addition to CYP2D6 genotype. Postoperative who received through patient-controlled analgesia were enrolled. Genotypes resulting 0, 1, or 2 alleles determined as well genotypes. primary endpoint 24-hour...
Organic cation transporter 1 (OCT1) is located in the sinusoidal membrane of human hepatocytes. It mediates uptake hydrophilic organic cationic drugs hepatocytes and thus determine their systemic concentrations. OCT1 has a broad spectrum structurally diverse substrates like metformin, sumatriptan, trospium, fenoterol. Recent cryo-EM data suggested that Y361, E386, R439, referred to as YER motif, could be important for transport. Building on this, we used extensive functional analyses...
The analysis of the available Corynebacterium genome sequence data led to proposal presence all three known pathways for trehalose biosynthesis in bacteria, i.e. synthesis from UDP-glucose and glucose 6-phosphate (OtsA-OtsB pathway), malto-oligosaccharides or alpha-1,4-glucans (TreY-TreZ maltose (TreS pathway). Inactivation only one by chromosomal deletion did not have a severe impact on C. glutamicum growth, while simultaneous inactivation OtsA-OtsB TreY-TreZ pathway resulted inability...
Methods for Cytochrome P450-2D6 (CYP2D6) genotyping are often time-consuming and laborious, which can restrict their use in pretherapeutic screening programs. Gene chip technology could overcome this problem. The aim of study was to evaluate CYP2D6 by a new improved gene compared PCR-RFLP method. AmpliChip CYP450 GeneChip® (AmpliChip) is microarray hybridization method CYP2C19. One hundred fifty-nine DNA samples were genotyped both as well and, where applicable, SNaPshot technique detects...
Carvedilol is an effective treatment in hypertension and chronic heart failure. The medical impact of polymorphisms CYP2D6 the β-adrenergic receptors ADRB1 ADRB2 on pharmacokinetics pharmacodynamics carvedilol controversial.After 25 mg was administered to 110 volunteers, concentrations were enantioselectively quantified effects resting exercise-induced rate blood pressure analyzed using population pharmacokinetic, pharmacodynamic pharmacogenetic modeling.There significant allele-specific...
Aim: To identify gene variants responsible for anthracycline-induced cardiotoxicity. Patients & methods: Polymorphisms of the NADPH oxidase subunits and anthracycline transporters ABCC1, ABCC2 SLC28A3 were genotyped in elderly patients (61–80 years) treated aggressive CD20+ B-cell lymphomas with CHOP-14 or without rituximab followed up 3 years. Results: The accumulation RAC2 subunit genotypes TA/AA among cases was statistically significant upon adjustment gender, age doxorubicin dose a...