Abstract：
PURPOSE:The aim of our study was to evaluate the impact of CYP3A4, CYP3A5, and ABCB1 polymorphisms on donepezil disposition and clinical outcome. METHODS:Fifty-four Italian patients diagnosed with probable mild to moderate Alzheimer's disease, treated with donepezil (37 patients 5 mg/day, 17 patients 10 mg/day) were genotyped for CYP3A4 (*1B, *3, and *4), CYP3A5 (*2, *3, and *6) and ABCB1 (3435C>T, 2677G>T/A, and 1236C>T) polymorphisms. All patients were evaluated for the degree of cognitive impairment with Mini Mental State Examination (MMSE) screening test at baseline (before treatment) and after at least 3 months of donepezil treatment at stable dose, when the drug plasma levels were measured. RESULTS:Three patients carried one detrimental CYP3A4 allelic variant, and 12 carried one functional CYP3A5*1 allele. No statistically significant association was found between CYP3A4 or CYP3A5 genotypes and plasma donepezil concentrations, or between genotypes and clinical response (as measured by change in MMSE score). Nine ABCB1 haplotypes were observed, the most common being 1236C/2677G/3435C (46%) and 1236T/2677T/3435T (41%). Patients homozygous for the T/T/T haplotype had slightly though not significantly lower plasma donepezil concentration-to-dose ratios than those carrying other genotypes [median (95% CI) 0.18 (0.13-0.45) vs. 0.31 (0.30-0.44) mg/l/mg/kg, respectively]. These patients also showed a slightly better clinical response (as measured by change in MMSE score) than the other genotype groups [median (95% CI) 0 (-1.3 to 3.3) vs. -1.0 (-2.1 to 0.0), respectively]. CONCLUSIONS:Our data suggest that the CYP3A4 and CYP3A5 polymorphisms are unlikely to influence donepezil metabolism and/or clinical outcome. On the other hand, the ABCB1 polymorphisms may play a role in donepezil disposition and clinical outcome.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Magliulo L,Dahl ML,Lombardi G,Fallarini S,Villa LM,Biolcati A,Scordo MGdoi
10.1007/s00228-010-0883-5subject
Has Abstractpub_date
2011-01-01 00:00:00pages
47-54issue
1eissn
0031-6970issn
1432-1041journal_volume
67pub_type
杂志文章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
更新日期：1992-01-01 00:00:00
abstract：:The effect of treatment with diflunisal on the steady-state pharmacokinetics of indomethacin has been studied in 16 healthy volunteers. The steady-state plasma concentration and AUC of indomethacin were significantly increased two- to threefold during treatment with diflunisal and its total clearance and total volume ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00558077
更新日期：1989-01-01 00:00:00
abstract：:The kinetics of mefloquine were studied in 12 healthy Thai male and 12 healthy Thai female volunteers. Mefloquine (MQ) was administered either alone (750 mg orally) or in combination (MSP) with sulphadoxine (1.5 g) and pyrimethamine (75 mg) to each of 6 male and 6 female subjects. Plasma concentrations of MQ were meas...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542191
更新日期：1987-01-01 00:00:00
abstract：PURPOSE:A population pharmacokinetic analysis was performed to define domperidone pharmacokinetic parameters in preterm neonates, as no pharmacokinetic data are available in this population. METHODS:An oral domperidone solution was administered (0.75 mg/kg per day) in 32 preterm neonates (64 samples). Domperidone plas...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-008-0535-1
更新日期：2008-12-01 00:00:00
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
更新日期：1986-01-01 00:00:00
abstract：OBJECTIVE:In order to document the stereoselective distribution in joints of a chiral nonsteroidal anti-inflammatory drug, the relative affinities of the enantiomers of tiaprofenic acid in synovium and for cartilage were compared. METHODS:The distribution of tiaprofenic acid in synovium and in cartilage was studied 25...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050109
更新日期：1996-01-01 00:00:00
abstract：:The present study was designed to investigate the effects of raised intragastric pH on the absorption of theophylline from a sustained-release formulation. Six healthy male volunteers participated in the cross-over randomised study and on one of two occasions were pretreated with 240 mg omeprazole, administered in thr...
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/BF01740660
更新日期：1992-01-01 00:00:00
abstract：PURPOSE:Fibroblast growth factor receptor 4 (FGFR4) expression has association with tumor malignancy. In thyroid cancers, FGFR4 has been reported to be characteristically expressed in aggressive thyroid tumors, such as anaplastic thyroid carcinoma (ATC). METHODS:We investigated FGFR4 expression in patients with ATC an...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-02842-y
更新日期：2020-05-01 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：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：PURPOSE:This study compares the in vivo relative lung bioavailability of Hydrofluoroalkane (HFA) Seretide delivered via unprimed and unwashed Aerochamber Plus (AP) or Volumatic (VM) spacers, a integrated breath-actuated vortex Synchro-Breathe (SB) device and an Evohaler pMDI (EH) device using adrenal suppression and ea...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-010-0989-9
更新日期：2011-04-01 00:00:00
abstract：:The purpose of this study was to examine the influence of cigarette smoking and gender on the pharmacokinetics of metoprolol. Eighteen volunteers with no evidence of clinical disease each randomly received the following doses of metoprolol tartrate: 100 mg orally, 200 mg orally and 20 mg as a constant-rate intravenous...
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/BF00637630
更新日期：1987-01-01 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：:The effect of a single oral dose of 40 mg xipamide on urinary excretion of Na+, K+, Cl-, Ca2+ and Mg2+ in healthy subjects and in patients with varying degrees of renal impairment was compared with various conventional diuretics. Xipamide caused marked excretion of Na+ and Cl-, whereas the diuretic produced only moder...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542150
更新日期：1984-01-01 00:00:00
abstract：:The effect of long-term treatment on the absorption and disposition of metoprolol has been evaluated in 8 healthy, non-smoking, elderly individuals (mean age 74.5 years) and in a control group of 8 healthy, young individuals. Two trace doses of [3H]metoprolol were given i.v., first concomitantly with a single oral 50 ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00544048
更新日期：1984-01-01 00:00:00
abstract：:The confidence interval approach to bioavailability assessment depends first on selection of the confidence level, usually 95%, and then determination of the confidence limits for the expected bioavailability ratio AUC(Test)/AUC(Reference). In practice, however, it is sometimes of greater interest to know the probabil...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00635713
更新日期：1985-01-01 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：: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 duration and extent of cardiac beta-blockade and their relationship to propranolol pharmacokinetics were assessed in nine healthy volunteers. Each subject received 160 mg of regular propranolol (R), 160 mg of sustained-release propranolol (SR) and no drug (control), both as single doses and once daily for 7 days. ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00637569
更新日期：1987-01-01 00:00:00
abstract：OBJECTIVE:Zuojin Pill has been shown to inhibit the cytochrome P450 (CYP) 2D6 isoenzyme in vitro. In Chinese individuals, CYP 2D6*10 is the most common allele with reduced enzyme activity. In this study, we investigated the pharmacokinetic interaction between Zuojin Pill and the sensitive CYP2D6 probe dextromethorphan ...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-016-2048-7
更新日期：2016-06-01 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：:Six children, aged 2 months - 4 years, received theophylline 5-6 mg/kg intravenously. Its disposition could be described by a two-compartment open model, the mean serum half life (t 1/2 beta) was 3.75 h, i.e., shorter than in adults, but there was a considerable interindividual variation (1.8-7.0 h, in one patient 13....
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00563120
更新日期：1979-09-01 00:00:00
abstract：:Encainide is a new anti-arrhythmic drug, which is highly effective against ventricular extrasystoles, both single and coupled, in the dose range of 80--140 mg i.v. Ventricular extrasystoles were abolished in 31 out of 33 cases treated. The drug is also relatively effective against supraventricular extrasystoles, but h...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00605629
更新日期：1979-11-01 00:00:00
abstract：:The role of acetylator phenotype in determining the response to hydralazine when it was added to diuretic and beta-blocker at doses not exceeding 200 mg daily was examined in 57 hypertensive patients. 81% of rapid acetylators needed 200 mg hydralazine daily compared to 38% of slow acetylators (p less than 0.01). Despi...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00546706
更新日期：1984-01-01 00:00:00
abstract：:The kinetics of 14C-metformin have been studied in five healthy subjects after oral and intravenous administration. The intravenous dose was distributed to a small central compartment of 9.9 +/- 1.61 (X +/- SE), from which its elimination could be described using three-compartment open model. The elimination half-life...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00562061
更新日期：1979-09-01 00:00:00
abstract：:The haemodynamic effects of concomitant intravenous administration of disopyramide (Norpace) and atenolol (Tenormin) were studied in a cross-over trial in 7 patients with ischaemic heart disease. Following 150 mg disopyramide i.v. the cardiac index (CI) and stroke volume index (SVI) decreased by 14% and 26%, respectiv...
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/BF00614295
更新日期：1986-01-01 00:00:00
abstract：:The pharmacokinetics and metabolism of quinidine were investigated in extensive and poor metabolisers of sparteine. No differences in plasma clearance, terminal half life, volume of distribution or cumulative urinary excretion of quinidine, 3-hydroxyquinidine and quinidine-N-oxide were observed between phenotypes. Thu...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00870989
更新日期：1986-01-01 00:00:00
abstract：:Information must be collected, evaluated and utilized to support every qualified activity. Medicine, with a written scientific tradition stretching back more than 2,000 years, is no exception. Here, we discuss a number of important items associated with the establishment of a drug information centre run by clinical ph...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-013-1484-x
更新日期：2013-05-01 00:00:00
abstract：:The effects on renal hemodynamics and salt-water handling of equipotent doses of the cardioselective beta-blocker metoprolol (M, 100 mg) and of the non-selective (intrinsic sympathetic activity) beta-antagonist pindolol (P, 10 mg) were compared in 30 WHO Grade 1-2 hypertensive men. M lowered pulse rate more than P. Sy...
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/BF00558292
更新日期：1989-01-01 00:00:00
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 frequencie...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-011-1065-9
更新日期：2011-11-01 00:00:00
