Abstract:
PURPOSE:The 388A>G and the 521T>C polymorphism of the SLCO1B1 gene affect the activity of the uptake transporter OATP1B1, thus influencing kinetics, safety, and efficacy of substrate drugs. To evaluate the impact of these polymorphisms in populations of different ethnic origins, it is important to know their frequencies and to develop fast and reliable methods for genotyping. We therefore established a new, high-throughput method and determined the genotype and allelic frequencies of these polymorphisms in Tanzanians, for which the frequencies were unknown thus far. METHODS:New LightCycler® 480-based methods with hybridization probes were established and used to genotype 366 Tanzanian and 236 European individuals for 388A>G (rs2306283) and 521T>C (rs4149056) in the SLCO1B1 gene. The methods were validated by direct sequencing of the polymerase chain reaction (PCR) products of heterozygous individuals and checked for intrarun precision repeatability, interrun precision reproducibility, robustness, and deviations from the Hardy-Weinberg equilibrium. RESULTS:The new methods allow unambiguous identification of the corresponding genotypes. There was a clear difference in allelic distribution between Tanzanians and Europeans, with the 388A>G (rs2306283) being much more prevalent in Tanzanians (87% vs 41%) and the 521T>C (rs4149056) being very rare in this African population (6% vs 17%). CONCLUSIONS:We developed robust and high-throughput methods to genotype common SLCO1B1 allelic variants with the LightCycler® 480. In Tanzanians, we identified the highest frequency of the 388A>G and 521T>C polymorphisms ever reported from black populations. The clinical relevance of SLCO1B1 genetic variation in the African population remains to be investigated.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Aklillu E,Mugusi S,Ngaimisi E,Hoffmann MM,König S,Ziesenitz V,Mikus G,Haefeli WE,Weiss Jdoi
10.1007/s00228-011-1065-9subject
Has Abstractpub_date
2011-11-01 00:00:00pages
1139-45issue
11eissn
0031-6970issn
1432-1041journal_volume
67pub_type
杂志文章abstract::The effect of the angiotensin converting enzyme inhibitor, perindopril, on autonomic function was assessed in a double blind, placebo controlled, crossover study in 10 normotensive males. Eight milligram of perindopril given orally lowered blood pressure without a change in heart rate. Perindopril enhanced the vagally...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00614298
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abstract::The effect of dexfenfluramine (dF) on body weight, blood pressure and noradrenergic activity were studied in 30 obese hypertensive patients randomly divided into two groups and treated for 3 months either with dF (30 mg daily; 16 subjects) or placebo (Pl; 14 subjects). 11 patients from the dF group and 9 patients give...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00265922
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abstract::The use of bioelectrical impedance (BI) analysis as a non-invasive approach for individualizing gentamicin therapy in newborn infants has been investigated in a two phase study. In Phase I, 1/impedance and length were identified as statistically significant predictors of the distribution volume of gentamicin (Adj R2 =...
journal_title:European journal of clinical pharmacology
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abstract::7-3H-phenylephrine was given to 15 volunteers by a short-infusion n = 4) or p.o. (10 volunteers, 1 patient with porto-caval anastomosis). Analysis of serum for free 3H-phenylephrine and fractionation of urinary radioactivity was performed by ion-exchange and thin-layer chromatography. As almost the same 3H-activity wa...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00637623
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abstract::We examined the pharmacokinetics of nifedipine after acute and sustained oral therapy and the potential haemodynamic interaction between nifedipine and sublingual nitroglycerin in nine patients with chronic stable angina. Nifedipine pharmacokinetics after a single oral dose and sustained dosing (three times daily for ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1987-01-01 00:00:00
abstract:OBJECTIVE:To analyse whether first-time use of antidepressants (incidence) and selection of TCAs (tricyclic antidepressants) versus new-generation drugs are associated with socio-economic status and psychiatric history. METHOD:We conducted a population-based cohort study using registry data covering Funen County, Denm...
journal_title:European journal of clinical pharmacology
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doi:10.1007/s00228-003-0723-y
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journal_title:European journal of clinical pharmacology
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doi:10.1007/s00228-020-02861-9
更新日期:2020-06-01 00:00:00
abstract::The role of mental stress in the development of hypertension and coronary heart disease remains uncertain. Its effects are likely to depend on an interaction of at least three factors: the nature of the stressor, its perception by the individual, and the individual's physiological susceptibility. This type of interact...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-01-01 00:00:00
abstract:OBJECTIVES:To evaluate the dose-response relationship of increasing doses of oxymetazoline compared with placebo in normal subjects, and to determine the sensitivities of rhinomanometry, acoustic rhinometry and symptoms in discriminating between differing doses of oxymetazoline in normal subjects. METHODS:The study ha...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s002280050665
更新日期:1999-09-01 00:00:00
abstract::A phamacokinetic study in man has been made of a new dosage form of diclofenac hydroxyethylpyrrolidine (DIEP); soluble salt packed in sachets was compared with diclofenac sodium as enteric coated tablets. Oral DIEP 2 X 50 mg showed a significant difference in absorption kinetics (ka, lag time and tmax) as compared to ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00265987
更新日期:1990-01-01 00:00:00
abstract:BACKGROUND:A four-drug cytochrome P450 (CYP) phenotyping cocktail was developed to rapidly and safely determine CYP2D6, CYP2C19, CYP2C9 and CYP1A2 enzyme activity and phenotype. METHODS:The cocktail consisted of the single CYP phenotyping probes of 50 mg tramadol (CYP2D6), 20 mg omeprazole (CYP2C19), 25 mg losartan (C...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-013-1561-1
更新日期:2013-12-01 00:00:00
abstract::The pharmacokinetics of ceftazidime have been investigated after single and multiple i.v. doses in 9 young healthy male volunteers and 15 elderly male patients with acute bacterial infections. All subjects had normal, age-correlated glomerular function. Distribution and elimination in young volunteers were unaffected ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00614556
更新日期:1988-01-01 00:00:00
abstract:OBJECTIVE:In Norway, very little data are available on the relation between the total number of research projects on the clinical development of drugs that have been started, the number of these projects in which the research phase has been completed and the number of projects for which results have been published. The...
journal_title:European journal of clinical pharmacology
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doi:10.1007/s00228-008-0601-8
更新日期:2009-03-01 00:00:00
abstract:PURPOSE:Our aim was to observe the impact of CYP3A4*1G genetic polymorphism on lipid-lowering efficacy of statins. METHODS:We studied 217 unrelated hyperlipidemic patients who prospectively received atorvastatin and 199 patients who received simvastatin as a single-agent therapy (20 mg day(-1) p.o.) for 4 weeks. Genot...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-008-0502-x
更新日期:2008-09-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315424
更新日期:1990-01-01 00:00:00
abstract:AIMS:To determine whether the variability in cytochrome P(450) (CYP)3A4 metabolic function is exhibited at both transcription and translation levels and to examine the population distribution of CYP3A4 enzyme kinetics, protein, and mRNA. METHODS:Enzyme kinetics of testosterone 6beta-hydroxylation, immunoblot CYP3A4 pr...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-002-0487-9
更新日期:2002-08-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00558240
更新日期:1988-01-01 00:00:00
abstract::Eleven patients with hepatic cirrhosis or cholestasis were treated with rifampicin for 7 to 132 days. Ten patients received hexobarbital (7.32 mg/kg) and five received tolbutamide (20 mg/kg) by i.v. infusion prior to and after rifampicin treatment; plasma concentrations of the two test compounds were determined during...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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journal_title:European journal of clinical pharmacology
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doi:10.1007/s00228-020-02936-7
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00561487
更新日期:1980-07-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-006-0225-9
更新日期:2007-01-01 00:00:00
abstract:PURPOSE:This study evaluated the benefits of and possible contraindications to warfarin treatment in patients with atrial fibrillation (AF) prior to the introduction of new oral anticoagulants using health registry data from inpatient care, specialist ambulatory care, and primary care. METHODS:This is a cohort study i...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-014-1739-1
更新日期:2014-12-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-009-0622-y
更新日期:2009-05-01 00:00:00
abstract:OBJECTIVE:Theophylline is metabolized to 1,3-dimethyluric acid (1,3-DMU), 3-methylxanthine, and 1-methylxanthine by CYP1A2 and partly by CYP2E1. Because 1,3-DMU is the major metabolite of theophylline, the 1,3-DMU/theophylline ratio is viewed as a good indicator of theophylline metabolic clearance. Here, we investigate...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-006-0165-4
更新日期:2006-08-01 00:00:00
abstract::6beta-Hydroxycortisol (6beta-OHF) urinary excretion has, for a long time, been considered a marker of drug induction and, more recently, of drug inhibition in humans and in laboratory animals, but its specificity is still under debate. In this work, we review 277 papers devoted to 6beta-OHF urinary excretion. We have ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-003-0690-3
更新日期:2003-12-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
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更新日期:2020-01-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-006-0174-3
更新日期:2006-10-01 00:00:00
abstract::Three groups of patients with biliary tract disease treated by cholecystectomy were given ceftriaxone. In Group 1 single doses of 150 mg and 1500 mg were given on Days 1 and 5 after cholecystectomy. In Group 2 2 g was given daily for 6 days and the cholecystectomy was on Day 2. Patients in Group 3 received 2 g every 1...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00607958
更新日期:1986-01-01 00:00:00
abstract:OBJECTIVE:To study the effect of cisplatin on plasma concentrations and urinary excretion of carnitine in ten patients with different malignancies treated with chemotherapy. METHODS:Carnitine concentrations were determined using a radioenzymatic assay and other metabolites by routine methods of clinical chemistry. Ren...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002280050504
更新日期:1998-09-01 00:00:00
abstract:OBJECTIVE:To examine the impact of medication and medical conditions on the fall risk in older hospitalized patients. DESIGN:Matched case-control study. SETTING:Large regional hospital in a mid-sized German city. SUBJECTS:Four hundred eighty-one inpatients aged ≥ 65 years who fell during hospitalization ("cases") an...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-019-02668-3
更新日期:2019-08-01 00:00:00