Abstract：
OBJECTIVE:Interindividual variability is common at all stages of drug absorption, distribution, pharmacodynamics, metabolism and elimination. In this study, we focused on two enzymes involved in phase-I drug metabolism as markers of pharmacological variability: the CYP3A and CYP2D6 subsystems of cytochrome P450. The main aim of our study was to determine whether substrate drugs for CYP2D6 and/or CYP3A enzymes, showing high interindividual matabolic variability, are more prone to postmarketing adjustments of defined daily dose (DDD). METHODS:A case-control design was used. We identified all DDD changes between 1982 and May 2004 through the website of the WHO Collaborating Centre for Drug Statistics Methodology. Cases were drugs with a DDD change and controls were other drugs with unchanged DDDs. Information about metabolism pathway, introduction year, literature exposure and administration route was retrieved. RESULTS:We included 88 cases and 176 controls. Of the 88 cases, 51 were dosage decreases (58.0%). Overall, DDD changes were not associated with CYP2D6/CYP3A metabolism (OR 1.92; 95%CI 0.78-4.72). However, DDD decreases were associated with CYP2D6/CYP3A metabolism (OR 3.21; 95%CI 1.25-8.26). Adjusting for introduction year weakened this effect (OR 2.78; 95%CI 0.98-7.90). CONCLUSION:Our study indicates that CYP2D6 and CYP3A substrates are more likely to require a DDD decrease after granting of market authorisation. However, this effect was diminished by adjusting for period of introduction. The implication of this finding is that variability indicators, as is demonstrated in this study for CYP2D6/CYP3A metabolism, can exert their influence on a wide variety of drug measures, such as the DDD.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Stolk P,Heerdink ER,Leufkens HGdoi
10.1007/s00228-005-0906-9subject
Has Abstractpub_date
2005-05-01 00:00:00pages
243-6issue
3eissn
0031-6970issn
1432-1041journal_volume
61pub_type
杂志文章abstract：:The effect of a single dose of carbamazepine (CBZ), 10 mg kg-1, on a battery of simple psychomotor tests was investigated in 12 healthy subjects (6 male, 6 female) in a balanced randomised double blind placebo controlled cross-over study. Psychomotor testing and blood sampling for total and free plasma CBZ, and CBZ 10...
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/BF00614193
更新日期：1986-01-01 00:00:00
abstract：:To assess the type and degree of innovation of the cardiovascular drugs centrally approved in the European Union between 1995 and 2002. Sources of information were the European Public Assessment Reports and the Summaries of Product Characteristics published by the European Medicines Evaluation Agency. The Agency appro...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-003-0634-y
更新日期：2003-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The purpose of this randomized, placebo-controlled, double-blind study was to investigate the preventive effect of topical administration of atorvastatin (ATV) on the acute radiation-induced skin toxicity in patients with breast cancer. PATIENTS AND METHODS:Seventy breast cancer patients were ra...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-018-2570-x
更新日期：2019-02-01 00:00:00
abstract：:The pharmacokinetics of mexiletine, a Class I antiarrhythmic drug, was investigated in 6 healthy volunteers after single oral doses and 15 min intravenous infusions of 3 mg/kg. Cimetidine and ranitidine are commonly used H2-receptor antagonists, which interact adversely with many drugs, e.g. inhibition of the metaboli...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00558298
更新日期：1989-01-01 00:00:00
abstract：:The relationship between the pharmacokinetics and pharmacodynamics of enoximone, a new positive inotropic agent, was investigated in 6 healthy men. The volunteers received single oral and i.v. doses of 3 and 1 mg/kg, respectively, and placebo in a double-blind cross-over trial. Plasma concentrations of enoximone and i...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00637599
更新日期：1988-01-01 00:00:00
abstract：PURPOSE:The role of pharmacogenomics, clinical and demographic parameters in pharmacokinetic predictions was evaluated in patients receiving mycophenolic acid (MPA). METHODS:A cohort study design of patients with glomerulonephritis secondary to lupus nephritis and anti-neutrophil cytoplasmic antibody (ANCA) vasculitis...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-010-0846-x
更新日期：2010-11-01 00:00:00
abstract：OBJECTIVE:The ABCB1 (MDR1) multidrug transporter plays a key role in determining drug bioavailability. Differences in drug response exist among different ethnic groups. However, until now, no haplotype data are available in a Black African population. METHODS:Exons 2, 7, 10, 11, 12, 14, 17, 21, 26, and the surrounding...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-004-0879-0
更新日期：2005-04-01 00:00:00
abstract：PURPOSE:Until recently, ondansetron was approved for the prevention of nausea and vomiting only in patients older than 2 years. However, as the use of ondansetron in patients younger than 2 years had been documented, characterization of ondansetron pharmacokinetics in this younger pediatric age group was warranted. ME...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1007/s00228-009-0730-8
更新日期：2010-01-01 00:00:00
abstract：:Clorazepate 20 mg was given i.m. to 49 mothers during the first stage of labour. The elimination of the drug was studied in 27 newborns produced by these mothers. The same dose was given to 13 women who underwent amniocentesis and to 7 women who were breast-feeding. "Total nordiazepam", i.e. the sum of clorazepate and...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00563103
更新日期：1979-04-17 00:00:00
abstract：PURPOSE:Few data on the efficacy and safety of drugs in children are available as in the past, these children were not included in randomized controlled trials (RCTs). Data on the efficacy and safety of drugs in children are extrapolated from adults. The EMA recognizes the need for long-term safety studies on various d...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-010-0930-2
更新日期：2011-05-01 00:00:00
abstract：PURPOSE:We examined the extent of concurrent use of antiplatelets, anticoagulants, or digoxin with Chinese medications (CMs) and identified its associated factors. METHODS:A retrospective cohort study was conducted using one million random samples from the Longitudinal Health Insurance Database 2005 in Taiwan. High-ri...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-012-1359-6
更新日期：2013-03-01 00:00:00
abstract：:Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration - time data were analysed by three different pharmacokinetic techniques. However as...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-01-01 00:00:00
abstract：PURPOSE:To evaluate the clinical relevance of the Janus Web Application (JWA) in screening for potential drug-drug interactions (DDIs). METHODS:One hundred and fifty patients taking two drugs or more were studied. Potential DDIs were identified by the JWA. Interviewing the patient and looking into his/her medical reco...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-008-0547-x
更新日期：2008-12-01 00:00:00
abstract：OBJECTIVE:NXY-059 is a nitrone-based, free-radical trapping agent being developed for the treatment of acute ischaemic stroke. Elimination of NXY-059 is primarily renal. The objective of the study was to investigate the pharmacokinetics of NXY-059 in subjects with renal impairment. METHODS:Twenty-four subjects with a ...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-002-0478-x
更新日期：2002-09-01 00:00:00
abstract：:Plasma concentrations of nitrazepam were measured by gas-liquid chromatography in: young healthy volunteers, in geriatric and psychiatric patients and in epileptic children. The disposition of nitrazepam was described in terms of a two-compartment open model. After a single oral dose of nitrazepam 5 mg the most promin...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00563100
更新日期：1979-04-17 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：PURPOSE:As an inhibitor of HMG-CoA reductase that catalyses the first step of cholesterol synthesis, pitavastatin undergoes little hepatic metabolism; however, it is a substrate of uptake and efflux transporters. Since pitavastatin is potentially co-administered with agents that affect transporter activities, the pharm...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-013-1554-0
更新日期：2013-11-01 00:00:00
abstract：PURPOSE:The aims of the present analysis were to determine prevalence of transaminase elevation in placebo-treated healthy volunteers in our historical phase I clinical trials and to assess which factors were associated with it. METHODS:We performed a retrospective analysis of alanine transaminase (ALT) levels in 481 ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-009-0684-x
更新日期：2009-10-01 00:00:00
abstract：PURPOSE:Higher drug concentrations in complex clinical scenarios in which multiple factors such as drug-drug interactions (DDIs) and comorbidities are simultaneously present are not necessarily rationalized in prospective clinical studies. Physiologically based pharmacokinetic (PBPK) modeling and simulation of the anti...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-02861-9
更新日期：2020-06-01 00:00:00
abstract：:The effect of cimetidine and ranitidine on doxepin pharmacokinetics was studied in 6 healthy volunteers. Each subject completed 3 study phases: Treatment A, 9 consecutive doses of 50 mg doxepin (once daily); Treatment B, same as Treatment A but co-administration of cimetidine 600 mg b.i.d. starting after the sixth dox...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542189
更新日期：1987-01-01 00:00:00
abstract：:The purpose of the study was to examine long-term nicotine substitution and its variability during use of a nicotine patch. In two smoking cessation studies a 16-h nicotine patch, releasing 15 mg nicotine, was applied daily for 16 h over 12 weeks, to 167 smokers. Salivary cotinine was highly correlated with plasma cot...
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/BF02280755
更新日期：1992-01-01 00:00:00
abstract：:The anti-ischaemic properties of nimodipine 30 mg and 60 mg t.i.d. for 4 days has been tested in a double-blind, placebo-controlled, cross-over study based on the use of hyperventilation to reduce flow velocity in cerebral arteries. Whether the anti-ischaemic properties were due to a vasodilatator action on cerebral b...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00315133
更新日期：1991-01-01 00:00:00
abstract：:The most important cardiovascular interactions between cardioactive drugs and monoamino-oxidase inhibitors or tricyclic antidepressants are reviewed. Post-ganglion blocking agents (e.g., guanethidine), clonidine, reserpine, and alpha-methyl-dopa should not be used in patients needing antide-present therapy. For hypert...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/BF00566537
更新日期：1977-01-01 00:00:00
abstract：OBJECTIVE:To evaluate the effect of the CYP2D6 genotype on the pharmacokinetics of tropisetron in healthy Korean subjects. METHODS:A single 5-mg capsule of tropisetron was administered orally to 13 healthy subjects. Plasma concentrations were determined by validated HPLC procedures and data were analyzed by using nonc...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-003-0595-1
更新日期：2003-06-01 00:00:00
abstract：:The effect of indenolol on heart rate and blood pressure at rest and after submaximal workload has been studied in 19 patients with established essential hypertension. A stepwise increase from moderate to submaximal exercise was chosen to mimic challenges normally occurring in daily life. After 4 weeks of once a day i...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00544058
更新日期：1985-01-01 00:00:00
abstract：:The concentrations of lormetazepam and its glucuronide in plasma and milk were determined during administration of 10 daily doses of lormetazepam 2 mg (2 tablets of Noctamid-1) to five mothers delivered by Caesarian section. Their babies were breast-fed throughout the study, and the plasma levels of lormetazepam and i...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542330
更新日期：1982-01-01 00:00:00
abstract：PURPOSE:To quantify the importance of drug-drug interactions (DDIs) in the occurrence of adverse drug reactions (ADRs) reported with serotoninergic reuptake inhibitors in a pharmacovigilance database. METHODS:All spontaneous reports of ADRs registered in 2008 by the Midi-Pyrénées PharmacoVigilance Centre that containe...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-011-1156-7
更新日期：2012-05-01 00:00:00
abstract：:The pharmacokinetics of intravenous chloramphenicol has been studied in 42 patients with liver disease and in 8 controls. The half-life of chloramphenicol (t 1/2) was increased in the various liver disorders, the metabolic clearance rate (MCR) and apparent volume of distribution (Vd) were decreased and the area under ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542103
更新日期：1981-01-01 00:00:00
abstract：OBJECTIVE:Lamotrigine as add-on treatment (500 mg per day) is effective in patients with refractory epilepsy, but its high cost requires a pharmacoeconomic analysis. We conducted a retrospective lifetime cost utility study in which clinical data were derived from a recent placebo-controlled clinical trial, cost-of-illn...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050402
更新日期：1998-02-01 00:00:00
abstract：:The debrisoquine hydroxylation phenotype was studied in 152 unselected healthy Tasmanian subjects, who were mostly Caucasians of British ancestry. Following a 10 mg oral dose of debrisoquine (D), the ratio of D/4-hydroxydebrisoquine excreted in 8-h urine (metabolic ratio, MR) was determined. MR values were bimodally d...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00315235
更新日期：1991-01-01 00:00:00
