Abstract:
AIM:Mizoribine (MZR) is an immunosuppressant for the prevention of allograft rejection in Asian countries, but the great variability in pharmacokinetics (PK) limits its clinical use. This study was to explore genetic and clinical factors that affect the MZR PK process. METHODS:Blood samples and clinical data were collected from 60 Chinese renal transplant recipients. MZR plasma concentration was measured at pre-dose (0 h) and 0.5, 1, 2, 3, 4, 5, 6, 8, and 12 h post-dose by high performance liquid chromatography with an ultraviolet detector. PK parameters were calculated by non-compartmental analysis. High-throughput sequenced single nucleotide polymorphism was applied screening possible genetic factors. RESULTS:Extensive inter-individual MZR PK differences were reflected in the process of elimination (ke, CL/F, MRT and t1/2) and intestinal absorption (Cmax and Tmax), as well as in the dose-normalized exposure (AUC0-12h/D). From 146 SNPs within 39 genes screened, AUC0-12h/D was found higher in recipients with CREB1 rs11904814 TT than with G allele carriers (3.135 ± 0.928 versus 2.084 ± 0.379 μg h ml-1 mg-1, p = 0.007). Recipients with SLC28A3 rs10868138 TT had lower t1/2 as compared to C allele carriers (0.728 ± 0.189 versus 0.951 ± 0.196 h, p = 0.001). Serum creatinine (SCr) explained 35.5% of C0/D variability (p < 0.001). Pure effects of genotypes CREB1 and SLC28A3 were 13.7% (p = 0.004) and 17.5% (p = 0.001) for AUC0-12h/D and t1/2, respectively. When additionally taking SCr into models, CREB1 and SLC28A3 genotypes explained 20.0% (p = 0.038) and 46.5% (p < 0.001) of AUC0-12h/D and t1/2 variability, respectively. CONCLUSION:CREB1 and SLC28A3 genotypes, as well as SCr, are identified as determinants in predicting inter-individual MZR PK differences in renal transplant recipients.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Dai R,Li J,Wu J,Fu Q,Yan J,Zhong G,Wang C,Chen X,Chen Pdoi
10.1007/s00228-020-02936-7subject
Has Abstractpub_date
2021-01-01 00:00:00pages
45-53issue
1eissn
0031-6970issn
1432-1041pii
10.1007/s00228-020-02936-7journal_volume
77pub_type
杂志文章abstract:PURPOSE:To investigate adherence rates to hospital drug formularies (HDFs) and cost of drugs in hospitals. METHODS:Data on drugs used during 2010 were analyzed for ten hospitals (two hospitals from each of the five regions), constituting 30 % of hospitals and 45 % of hospital beds in Denmark. Drug use data from indivi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-013-1540-6
更新日期:2013-10-01 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:OBJECTIVE:More than 11% of the Caucasian population are heterozygous or homozygous carriers of thiopurine S-methyltransferase (TPMT) mutants and are at risk for toxic side effects when treated with thiopurine drugs. Therefore, screening for TPMT polymorphisms in a patient prior to prescribing these agents is recommende...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-004-0728-1
更新日期:2004-03-01 00:00:00
abstract:OBJECTIVES:To investigate the risk factors for noncompliance in elderly home-care recipients; and to evaluate to what extent regular home visits and drug counseling by a pharmacist contribute to compliance. SUBJECTS:One hundred and sixty-three elderly home-care recipients aged 62 years and over took part in this study...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050609
更新日期:1999-04-01 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:PURPOSE:Pharmacology and pharmacotherapy education is being increasingly integrated in medical curricula, which might lead to a specific loss of knowledge in these subjects. This, in turn, could lead to harmful prescribing errors, especially in vulnerable older patients. METHODS:Teachers who coordinated education in D...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1830-2
更新日期:2015-05-01 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::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::The pharmacokinetic behaviour of cefadroxil was dose-dependent in healthy male volunteers following the oral administration of single doses of 5, 15, and 30 mg.kg-1. As the dose of cefadroxil increased from 5 to 15 and 30 mg.kg-1, the peak plasma concentrations, normalized to 5 mg.kg-1, decreased significantly from 15...
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/BF00265914
更新日期:1991-01-01 00:00:00
abstract::In 8 healthy subjects the absorption of cimetidine was investigated when given alone, together with 60 ml aluminium/magnesium hydroxide containing antacid (neutralising capacity 26 mmol HCl/10 ml), and together with liquid metoclopramide 14 mg. The antacid significantly (P less than 0.01) reduced the bioavailability (...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00544602
更新日期:1981-01-01 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
abstract:INTRODUCTION:Body position may influence physiological characteristics, such as perfusion, gastrointestinal function and plasma volume. These characteristics may interact with key factors determining the pharmacokinetics of drugs (dissolution, absorption, distribution, metabolism, excretion). OBJECTIVES:Based on a sys...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-008-0579-2
更新日期:2009-02-01 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::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::In order to assess whether dinnertime administration of a once daily dose of famotidine is more advantageous than a bedtime dose in suppressing evening and nocturnal gastric acidity, we gave nine patients with a past history of duodenal ulcer in double-blind, randomized fashion either (1) placebo at 6 p.m. and 10 p.m....
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/BF00609254
更新日期:1988-01-01 00:00:00
abstract:AIM:It has been reported that verapamil and atorvastatin are inhibitors of both P-glycoprotein (P-gp) and microsomal cytochrome P450 (CYP) 3A4, and verapamil is a substrate of both P-gp and CYP3A4. Thus, it could be expected that atorvastatin would alter the absorption and metabolism of verapamil. METHODS:The pharmaco...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-007-0447-5
更新日期:2008-05-01 00:00:00
abstract::Atenolol 100 mg and penbutolol 40 mg given once a day were both effective in controlling moderate hypertension, as judged by a randomised controlled, double-blind trial in 45 patients treated for six weeks. Both drugs significantly reduced the resting supine and erect blood pressures. No serious adverse effects could ...
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/BF00637507
更新日期:1981-01-01 00:00:00
abstract::There is conflicting data in the literature as to whether subsensitivity of in-vivo beta 2-adrenoceptor (beta 2-AR) responses in patients with asthma is due to an endogenous defect of beta 2-AR or an effect of exogenous beta 2-agonist therapy. The purpose of the study was to compare in-vitro parameters of lymphocyte b...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315310
更新日期:1993-01-01 00:00:00
abstract::A questionnaire survey was carried out to explore differences in the approach to treatment of patients with Type II diabetes between physicians in Northern Ireland, Norway and Sweden, and to discover to what extent it could account for the three-fold difference in drug use between the countries. A representative sampl...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542408
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:OBJECTIVE:Contraception is recommended for female patients during ursodeoxycholic acid (UDCA) treatment for the potential teratogenic effect of this bile acid, and the aim of our study was to determine whether this treatment affects the bioavailability of ethinylestradiol (EE2). METHODS:In this double-blind, randomise...
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/s00228-004-0796-2
更新日期:2004-09-01 00:00:00
abstract:BACKGROUND:Cytochrome P450 2C9 (CYP2C9) allelic variant carriers have been shown to experience hyper-responsiveness to small doses of oral anticoagulants (OAs) (warfarin or acenocoumarol) and a higher bleeding rate. OBJECTIVES:To determine the relative frequencies of different risk factors for OA overdose including di...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-002-0538-2
更新日期:2003-03-01 00:00:00
abstract::An analytical procedure for the simultaneous determination of pethidine and its N-Demethylated metabolite, norpethidine, in plasma is described. Pethidine and norpethidine are separated by partition chromatography, converted to the trichloroethyl carbamate with trichloroethyl chloroformate and determined by electron c...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00561790
更新日期:1977-01-01 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::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::Since 1988, the German Embryotox institute combines individual counselling of pregnant women and their health care providers (HCP) with research on drug safety in pregnancy. In addition, Embryotox offers web-based information which covers the most important and most frequently requested pharmaceutical substances. In c...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-017-2351-y
更新日期:2018-02-01 00:00:00
abstract::The biliary excretion of mebendazole has been investigated in two patients to whom it was given for the treatment of echinococcosis, although it was found to be only partly effective. Oral mebendazole was extensively metabolized and the conjugated parent substance and its metabolites were excreted in the bile. One pat...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00544020
更新日期:1983-01-01 00:00:00
abstract::Naftopidil exerts its antihypertensive action via alpha 1-adrenoceptor blockage and Ca2+ antagonism in vascular smooth muscle. Since the chemically similar 1-(1-naphthyl) piperazine is known to be a 5-hydroxytryptamine2 receptor antagonist, the 5-hydroxytryptamine (5-HT) antagonistic properties of naftopidil were test...
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/BF00192561
更新日期:1994-01-01 00:00:00
abstract::We have evaluated the pharmacokinetics of high doses of clonidine, as used in the prophylactic treatment of alcohol withdrawal syndrome, in 11 alcohol-dependent patients undergoing surgery for oesophagogastrectomy. Clonidine was given in a bolus of 150 micrograms followed by a continuous infusion. After a mean period ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315500
更新日期:1993-01-01 00:00:00
abstract::Total beta-adrenoceptor density and beta 1- and beta 2-subtype distribution in right and left atria and in different ventricular regions from 14 failing and seven nonfailing human hearts have been compared. End-stage heart failure was due to idiopathic dilated cardiomyopathy (n = 8) or ischaemic cardiomyopathy (n = 6)...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00265923
更新日期:1992-01-01 00:00:00