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 (CYP2C9) and 200 mg caffeine (CYP1A2) and was administered as a single oral dose. For enzyme activity measurements, urine was collected as 8 h post-administration and blood was sampled at 4 h. The enzyme activity was determined by metabolic ratios of molar concentrations of the drugs and their enzyme catalyzed metabolites and was correlated to the relevant genotypes. RESULTS:In a pilot study in 12 healthy male volunteers the CYP genotype-phenotype correlation and robustness of the cocktail was successfully determined without detection of any adverse drug reactions. In the subsequent population study, four female volunteers experienced unexpected and unacceptable moderate and severe adverse reactions (ARs) of headache, dizziness, nausea, vomiting, blue fingers, nails and lips and difficulties in urinating, which led to the study being prematurely terminated after inclusion of only 22 subjects (15 males, 7 females) [corrected]. CONCLUSION:Attention must be paid to adverse reactions when designing new combinations of phenotype cocktails regardless of the doses and drugs involved. We specifically warn against the combination of tramadol, omeprazole, losartan and caffeine.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Pedersen RS,Damkier P,Christensen MM,Brosen Kdoi
10.1007/s00228-013-1561-1subject
Has Abstractpub_date
2013-12-01 00:00:00pages
1997-9issue
12eissn
0031-6970issn
1432-1041journal_volume
69pub_type
临床试验,杂志文章abstract：OBJECTIVE:Entacapone is a peripherally acting catechol O-methyltransferase (COMT) inhibitor used as an adjunct to each daily levodopa/dopa decarboxylase (DDC) inhibitor dose in the treatment of Parkinson's disease. Parkinsonian patients with advanced disease and motor fluctuations take several doses of levodopa daily, ...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s002280050657
更新日期：1999-08-01 00:00:00
abstract：OBJECTIVE:To determine the variability of coumarin 7- and 3-hydroxylation in a human population and to evaluate the evidence for the existence of genetic polymorphism in these pathways. 7-Hydroxylation of coumarin is considered to be a detoxication pathway, whilst 3-hydroxylation, which predominates in rats, leads to h...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050489
更新日期：1998-07-01 00:00:00
abstract：:The pharmacokinetics of i.v. chloramphenicol succinate and oral chloramphenicol palmitate were studied in Ethiopian children with different nutritional states. In children with kwashiorkor the plasma clearance of chloramphenicol was significantly lower than in children of normal weight (4.16 ml/min/kg versus 7.53 ml/m...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00607094
更新日期：1983-01-01 00:00:00
abstract：:The hypocholesterolemic cation resins, cholestyramine and colestipol, have variable effects on the absorption parameters of a number of lipophillic, anion drugs. Because of the unpredictable nature of this interaction, we have assessed in human volunteers the effect of these resins on the rate and total absorption of ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542221
更新日期：1983-01-01 00:00:00
abstract：OBJECTIVE:Thiopurine drugs are commonly used in pediatric patients for the treatment of acute leukemia, organ transplantation and inflammatory diseases. They are catabolized by the cytosolic thiopurine methyltransferase (TPMT), which is subject to a genetic polymorphism. In children, enzyme activities are immature at b...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-004-0732-5
更新日期：2004-04-01 00:00:00
abstract：PURPOSE:Tolvaptan is a selective vasopressin V2 receptor antagonist that can be given orally once daily for treatment of clinically significant hypervolemic and euvolemic hyponatremia (US and Europe) or extracellular volume expansion despite taking other diuretics (Japan). In vitro studies indicated that tolvaptan was ...
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/s00228-011-1106-4
更新日期：2012-02-01 00:00:00
abstract：:Twenty patients (5 females, 15 males) with severe heart failure (NYHA IV), due to coronary artery disease in 14, and congestive cardiomyopathy in 6, received an intravenous bolus of the calcium blocker nisoldipine 0.2 mg followed by a continuous infusion of 0.2 micrograms.kg-1.min-1. Haemodynamic measurements were per...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00314795
更新日期：1990-01-01 00:00:00
abstract：PURPOSE:The present study was carried out in order to assess the effects of chronic administration of flunitrazepam (as an oral hypnotic) on 24-h blood pressure (BP) and heart rate (HR) in healthy young adults. MATERIALS AND METHODS:Following a 2-week placebo run-in period, 28 healthy volunteers (13 males and 15 femal...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-018-2466-9
更新日期：2018-08-01 00:00:00
abstract：OBJECTIVE:In a double blind, randomised, placebo-controlled, cross-over study 12 healthy male volunteers were allocated to receive felodipine + placebo, cyclosporine + placebo, and felodipine + cyclosporine in order to investigate the interaction between the calcium channel blocker felodipine and cyclosporine as it aff...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s002280050093
更新日期：1996-01-01 00:00:00
abstract：:The time-courses of plasma carbamazepine concentrations were followed in six apparently healthy adult subjects who, at different times, took single oral drug doses of 200, 400, 500, 600, 700, 800 and 900 mg. There were some suggestions of impaired bioavailability of the drug when given in tablet form. The following va...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00561065
更新日期：1977-12-28 00:00:00
abstract：:Dexmedetomidine is a novel alpha 2-adrenoceptor agonist that may provide beneficial effects as premedication for anesthesia. The pharmacokinetics and pharmacodynamics of transdermal (TD) and intravenous (i.v.) dexmedetomidine were studied in nine healthy male subjects in a crossover trial. The TD preparation, containi...
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/BF00194403
更新日期：1994-01-01 00:00:00
abstract：:The pharmacokinetics of ethanol in plasma and whole blood have been investigated and the results used to estimate the volume of total body water (TBW) by means of the dilution principle. Fifteen men (mean age 62 y) were given 0.6 g ethanol/kg body weight as an intravenous infusion over 1 h. The peak concentration of e...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00280133
更新日期：1992-01-01 00:00:00
abstract：BACKGROUND:Many studies have indicated the adequate use of lipid-lowering drugs (LLDs) as a factor in reducing the risk of cardiovascular disease. However, in clinical practice, a very high percentage of patients are not adequately treated. OBJECTIVE:To analyze the management of hypercholesterolemia in a non-experimen...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-005-0911-z
更新日期：2005-05-01 00:00:00
abstract：:Plasma renin concentration (PRC) was measured in 46 patients with essential hypertension before and after treatment for 4 weeks with alprenolol 600-1200 mg daily. In 27 of these patients PRC was measured after 4 weeks of combined treatment with alprenolol and hydralizine. During alprenolol treatment PRC and blood pres...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00645128
更新日期：1977-10-14 00:00:00
abstract：OBJECTIVE:This paper describes a method to determine the number of patients and the number of blood levels which are appropriate for a pharmacokinetic population analysis. METHODS:We studied this question by performing 203 runs of population analysis, using the NPEM algorithm with a one compartment model, starting wit...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050199
更新日期：1996-01-01 00:00:00
abstract：PURPOSE:Spontaneous reporting systems in European countries are crucial for collecting adverse drug reaction (ADR) reports. The aim of this study was to evaluate reporting activity among countries and their strategy to increase the number of reports. We also established the best measure for assessment quantity of repor...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-012-1219-4
更新日期：2012-07-01 00:00:00
abstract：OBJECTIVE:To investigate if an intervention aimed at improving the quality of the diagnostic procedures in Spanish general practice could lower antibiotic prescribing in patients with respiratory tract infections (RTIs). METHODS:GPs in the intervention group (n=17) registered all patients with RTIs during a 3-week per...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-006-0187-y
更新日期：2006-11-01 00:00:00
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
doi：10.1007/BF00637629
更新日期：1987-01-01 00:00:00
abstract：PURPOSE:In the management of melanoma, BRAF inhibitors yield fast disease control; however, the duration of response does not last very long. Ipilimumab-an anti-CTLA4 antibody on the other hand-provides longer-lasting results of treatment but achieves less favorable responses. The aim of this study was to assess the ef...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-018-2590-6
更新日期：2019-03-01 00:00:00
abstract：:The effects of intravenous strophanthin K (0.125 and 0.25 MG) and lanatoside C (0.4, 0.8 and 1.6 mg) on systolic time intervals (STI) and impedance plethysmographic (IP)P values were studied in ten patients with compensated coronary heart disease. The heart rate decreased significantly during a two-hour study in the l...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00613426
更新日期：1975-10-10 00:00:00
abstract：PURPOSE:The present study was carried out to investigate current prescribing and dispensing practices in the largest two teaching hospitals in Sudan and compare them with those of published studies in developing countries. METHODS:A descriptive, quantitative and cross-sectional study was conducted among hospital outpa...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-006-0216-x
更新日期：2006-12-01 00:00:00
abstract：:The pharmacokinetics of naproxen have been examined in 13 elderly patients (mean age 84.2 years) and in 9 younger patients (mean age 53.9 years) at the end of a 21 day course of therapy with naproxen 500 mg b.d. The mean pre-dose concentration on days 19, 20 and 21 was significantly higher in the elderly patients than...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00613525
更新日期：1986-01-01 00:00:00
abstract：:The blood level versus time curve for unchanged cimetidine after a 200 mg oral dose has been determined in 20 apparently healthy subjects, ranging from 22 to 84 years of age. A significant relationship between the area under the curve (AUC) and age was found (r = 0.81; P less than 0.001). The peak concentrations of ci...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00618514
更新日期：1979-05-21 00:00:00
abstract：:The frequency distribution of the 8-h urinary ratio of log metoprolol/alpha-hydroxymetoprolol was assessed in 65 healthy, unrelated Jordanian volunteers. There was no apparent bimodality in the frequency distribution of this ratio among the subjects studied. The frequency of the poor metabolizer phenotype of metoprolo...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00191160
更新日期：1994-01-01 00:00:00
abstract：:An open, dose-titration study of alfuzosin, a new selective post-synaptic alpha 1-adrenoceptor antagonist with additional direct vasodilator properties has been performed. After a 3-week run-in placebo period, 12 patients with essential hypertension received alfuzosin 5 mg oral b.d., and then the dose was doubled ever...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00555503
更新日期：1988-01-01 00:00:00
abstract：OBJECTIVE:To determine the pharmacokinetics and organ distribution of i.v. and oral methylene blue, which is used to prevent ifosfamide-induced encephalopathy in oncology. METHODS:The concentration of methylene blue in whole blood was measured using high-performance liquid chromatography in seven volunteers after i.v....
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280000124
更新日期：2000-06-01 00:00:00
abstract：:Since little is known of the number and types of binding sites on alpha 1-acid glycoprotein (AAG) and because drug-drug protein binding interactions often fail to fit a simple model, a study of the effect of 9 known AAG binding drugs on lidocaine free fraction (LFF) was performed. Serum was obtained from 10 healthy ma...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF01037957
更新日期：1983-01-01 00:00:00
abstract：:The disposition of paracetamol following an oral dose of 1.0 g was compared in 10 healthy volunteers, 7 patients with moderate chronic renal failure and 6 patients with end stage renal failure on maintenance haemodialysis. Paracetamol absorption was normal in the patients with renal failure. The mean plasma half-life ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00558162
更新日期：1989-01-01 00:00:00
abstract：:The pharmacokinetics of a single dose of netilmicin (NM) was studied in 6 healthy volunteers. Elimination of the drug was followed in serum and urine for 24 h and 72 h, respectively. NM concentrations were measured with a modified radioenzymatic assay. A three compartment open model was employed to calculate the pharm...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00605631
更新日期：1979-11-01 00:00:00
abstract：OBJECTIVES:To compare the systemic exposure for intranasal mometasone furoate (MF) and fluticasone propionate (FP) aqueous nasal sprays (ANS) in terms of serum and urinary cortisol parameters and plasma pharmacokinetics. METHODS:Twelve healthy subjects completed this three-way, cross-over study. They received FPANS (5...
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/s00228-004-0763-y
更新日期：2004-06-01 00:00:00
