Abstract：
OBJECTIVES:Digoxin is a well-known probe for the activity of P-glycoprotein. The objective of this work was to apply different methods for covariate selection in non-linear mixed-effect models to study the relationship between the pharmacokinetic parameters of digoxin and the genotype for two major exons located on the multi-drug-resistance 1 (MDR1) gene coding for P-glycoprotein. METHODS:Thirty-two healthy volunteers were recruited in three pharmacokinetic drug interaction studies. The data after a single oral administration of digoxin alone were pooled. All subjects were genotyped for the MDR1 C3435T and G2677T/A genotypes. The concentration-time profile of digoxin was established using 12-16 blood samples taken between 15 min and 72 h after administration. We modelled the pharmacokinetics of digoxin using non-linear mixed-effect models. Parameter estimation was performed using the stochastic approximation EM method (SAEM). We used three methods to select the covariate model: selection from a full model using Wald tests, forward inclusion using the log-likelihood ratio test and model selection using the Bayesian Information Criterion. RESULTS:The three covariate inclusion methods led to the same final model. Carriers of two T alleles for the C3435T polymorphism in exon 26 of MDR1 had a lower apparent volume of distribution than carriers of a C allele. The only other covariate effect was a shorter absorption time-lag in women. CONCLUSION:The apparent volume of distribution of digoxin is lower in TT subjects, probably reflecting differences in bioavailability. Non-linear mixed-effect models can be useful for detecting the influence of covariates on pharmacokinetic parameters.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Comets E,Verstuyft C,Lavielle M,Jaillon P,Becquemont L,Mentré Fdoi
10.1007/s00228-007-0269-5subject
Has Abstractpub_date
2007-05-01 00:00:00pages
437-49issue
5eissn
0031-6970issn
1432-1041journal_volume
63pub_type
杂志文章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
abstract：PURPOSE:The aim of this study was to examine whether educational meetings and group detailing could increase the use of drugs from the ward lists or the drug formulary in hospitals. METHODS:Twelve medical wards from two hospitals were randomized into three groups: control, basic and extended intervention. All wards ha...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-013-1589-2
更新日期：2014-01-01 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：:Piretanide 60 mg was administered intravenously over 30 min to 15 men with different degrees of renal failure. The mean piretanide serum concentration at the end of the infusion period was 5.72 +/- 1.51 micrograms/ml. Serum piretanide concentration-time curves declined biexponentially and 24 hours after medication the...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00544091
更新日期：1985-01-01 00:00:00
abstract：:The mode and site of action of the new diuretic agent piretanide were investigated in man. The effect of a single oral dose of 12 mg was compared with that of furosemide 80 mg p.o. iin 6 patients with the nephrotic syndrome. Piretanide showed a greater diuretic and natriuretic response than furosemide during maximal w...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00561895
更新日期：1980-01-01 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：:Some physicians regard patients of Geriatric Units as a homogeneous population with respect to digoxin dosage requirements. Others advocate the use of pharmacokinetic models in prescribing digoxin for the elderly. Sixty in-patients of Geriatric Units were studied and the results compared with those previously obtained...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF02455997
更新日期：1987-01-01 00:00:00
abstract：PURPOSE:Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor, widely prescribed for type 1 human immunodeficiency virus infection. A small proportion of individuals treated with NVP experience severe cutaneous adverse events, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)....
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-013-1549-x
更新日期：2013-11-01 00:00:00
abstract：BACKGROUND:Tamoxifen is one of the cornerstones of endocrine therapy for breast cancer. Recently, the decreased activity CYP3A4*22 allele and the loss of function CYP3A5*3 allele have been described as potential factors that could help to explain the inter-patient variability in tamoxifen metabolism. The aim of this st...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-017-2323-2
更新日期：2017-12-01 00:00:00
abstract：OBJECTIVE:The influence of nevirapine (NVP) on lopinavir (LPV) pharmacokinetics was investigated by a population analysis based on a non-linear mixed-effect modelling method. METHODS:In this analysis, 95 HIV-1 infected patients were studied [52 treated with LPV/ritonavir (400/100 mg twice a day) plus nucleoside revers...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-005-0900-2
更新日期：2005-04-01 00:00:00
abstract：OBJECTIVE:Losartan was given to subjects with known phenotypes of the polymorphic enzymes CYP2D6 and CYP2C19 to study any possible influence on the metabolism of the drug. METHODS:Plasma concentrations of losartan and E-3174 were studied after oral intake of 50 mg losartan in 24 healthy, male, Swedish Caucasian subjec...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050629
更新日期：1999-06-01 00:00:00
abstract：:The effect of the GABAergic drug sodium valproate (SV) on the exercise-induced release of growth hormone (GH) was investigated in 10 healthy males. The exercise test consisted of using a stationary bicycle ergometer at 450 kg/min for 20 min. SV 600 mg blunted the increase in GH induced by the exercise, suggesting GABA...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00544075
更新日期：1985-01-01 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:Tolcapone is an efficacious catechol-O-methyltransferase inhibitor for Parkinson's disease (PD). However, safety issues hampered its use in clinical practice. We aimed to provide evidence of safety and efficacy of tolcapone by a systematic literature review to support clinicians' choices in the use of an enlarg...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-020-03081-x
更新日期：2021-01-07 00:00:00
abstract：OBJECTIVE:After liver transplantation (LT), genotypic differences between the recipient and the transplanted liver, medications and post-LT complications may all affect drug metabolism. We have studied the effect of two CYP2D6 mutations in the donor and the recipient on post-LT CYP2D6 phenotype. METHOD:The CYP2D6 phen...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050419
更新日期：1998-03-01 00:00:00
abstract：:The effects of an oral dose of atropine (0.03 mg/kg body weight) and an IM (0.02 mg/kg) dose on the heart rate and salivary flow in seven healthy adult volunteers were compared to see whether the oral dose was sufficient to inhibit vagal reflexes of the heart. Atropine concentrations in plasma were determined by an M2...
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/BF00192357
更新日期：1995-01-01 00:00:00
abstract：OBJECTIVES:The objective of this study was to describe determinants of current and subsequent benzodiazepine use in an elderly population, the Paquid cohort. METHODS:The study was conducted on a cohort of 2,792 community-dwelling subjects 65 years of age or more living in the Gironde department, southwestern France. B...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280100326
更新日期：2001-08-01 00:00:00
abstract：PURPOSE:The aim of this study is to validate medication proxies for the identification of children diagnosed with atopic disorders that can be applied in various types of epidemiological research. METHODS:Records of 7439 children, aged between 0 and 10 years, in the period 2001 until 2010, were retrieved from the Regi...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-015-1940-x
更新日期：2016-01-01 00:00:00
abstract：:A new acid thiol, 2-mercaptopropionate, has been identified by GC-MS in urine from cystinuric patients on treatment with 2-mercaptopropionylglycine. The amount excreted was 50-300 mumol/24h and it was correlated with the oral dose of 2-mercaptopropionyl-glycine. The observation may be of clinical importance as the met...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00871000
更新日期：1986-01-01 00:00:00
abstract：:The cardiovascular and endocrine profile of cromakalim has been studied in 8 healthy men (age 25 +/- 2 years: means SEM) and its influence on renin release from cultured rat juxtaglomerular cells in vitro has also been examined. According to a double-blind, randomized sequence the subjects received placebo or cromakal...
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/BF00558067
更新日期：1989-01-01 00:00:00
abstract：:As a target group, geriataric patients were selected for pharmacokinetic studies with terodiline (Mictrol), an anticholinergic and calcium antagonist drug effective in the treatment of urinary incontinence. The single-dose kinetics in the geriatric patients (mean age 82 years) differed significantly from that previous...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00540958
更新日期：1988-01-01 00:00:00
abstract：:Blood ciclosporin (Cs) metabolite pattern in 58 liver grafted patients was routinely monitored by HPLC from the first Cs dose after transplantation until discharge from hospital. Eighteen patients with normal kidney function were allocated to Group I and 14 patients in Group II suffered Cs nephrotoxicity during their ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00314953
更新日期：1991-01-01 00:00:00
abstract：:The pharmacokinetics of lorazepam was examined in 10 male patients with insulin-dependent diabetes mellitus before and following treatment with neomycin and cholestyramine. Neomycin and cholestyramine were given in an attempt to block the enterohepatic circulation of lorazepam and so to permit an in vivo estimate of h...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00198307
更新日期：1995-01-01 00:00:00
abstract：PURPOSE:The study aims to analyse overall as well as subgroup-specific outpatient paediatric macrolide use in five European countries, including time trends of macrolide prescription rates, and to provide potential targets for future interventions aiming to promote judicious macrolide use. METHODS:Macrolide prescripti...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-015-1870-7
更新日期：2015-08-01 00:00:00
abstract：PURPOSE:Methylenedioxymethamphetamine (MDMA, ecstasy) is used recreationally and frequently leads to sympathomimetic toxicity. MDMA produces cardiovascular and subjective stimulant effects that were shown to partially depend on the norepinephrine transporter (NET)-mediated release of norepinephrine and stimulation of α...
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/s00228-017-2392-2
更新日期：2018-03-01 00:00:00
abstract：BACKGROUND AND OBJECTIVES:Opicapone is a novel third generation catechol-O-methyltransferase (COMT) inhibitor. The purpose of this study was to compare the levodopa pharmacokinetic profile throughout a day driven by the COMT inhibition either following repeated doses of opicapone or concomitant administration with enta...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-014-1701-2
更新日期：2014-09-01 00:00:00
abstract：:The duration of action of tiapamil was assessed in ten patients with stable exertional angina. Maximal symptom-limited treadmill exercise electrocardiography was performed before and at 1, 3, 6 and 9 h after therapy. Significant differences were only found at 1 h after tiapamil with increases in mean exercise duration...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00543965
更新日期：1987-01-01 00:00:00
abstract：BACKGROUND:Visual hallucinations (VHs) are frequent non-motor complication of Parkinson's disease (PD), associated to a negative prognosis. Previous studies showed an association between dopamine receptor (DR) gene (DR) variants and psychosis in Alzheimer's disease, addictions, schizophrenia, and bipolar disorder. Howe...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-016-2111-4
更新日期：2016-11-01 00:00:00
abstract：OBJECTIVE:To describe trends in opioid consumption in Israel (morphine, methadone, oxycodone, pethidine, fentanyl, buprenorphine, codeine, and dextropropoxyphene) over the 9 years, 2000-2008, and to explore explanations for changes in consumption, in amounts and the pattern. METHODS:Data for the 2000-2008 period (all ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-010-0932-0
更新日期：2011-02-01 00:00:00
abstract：OBJECTIVE:We recently reported a highly stereoselective increase in plasma concentrations of (S)-atenolol during exercise which is most likely due to a release of the drug from adrenergic cells. The objective of the present study was to investigate the influence of physical exercise on plasma concentrations of the (R)-...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050119
更新日期：1996-01-01 00:00:00
