Abstract：
PURPOSE:Although CYP3A4/5 enzymes play the predominant role in the metabolism of simvastatin and lovastatin, polymorphisms in CYP2D6 were reported to be associated with the cholesterol-lowering effect and/or tolerability of simvastatin. This study was performed to examine whether common CYP2D6 polymorphisms affect the pharmacokinetics of lovastatin, which is taken as the inactive prodrug lovastatin lactone and converted to active lovastatin acid. METHODS:A single-dose pharmacokinetic study was performed with lovastatin in 23 Chinese healthy male subjects. Plasma concentrations of lovastatin lactone and acid were determined by an LC-MS-MS method in samples collected over 24 h after single oral doses of 40-mg lovastatin. RESULTS:Compared with the CYP2D6 wt/wt group, the area under the plasma concentration-time curve (AUC(0-∞)) values for lovastatin lactone increased (P < 0.01) by average ratios (95% CI) of 1.57 (1.01-2.45), 2.11 (1.36-3.29), 2.52 (1.47-4.32), and 5.84 (3.16-10.78) in the wt/*10, *10/*10, *10/*5, and *5/*5 groups, and the values of lovastatin lactone plasma clearance (CL/F) were reduced on average (95% CI) by 40.4% (10.2-60.5%), 53.1% (29.3-68.9%), 63.8% (40.2-78.1%) and 84.2% (72.1-91.1%) in these genotype groups respectively. The pharmacokinetics of lovastatin acid did not differ among the genotype groups. CONCLUSION:This study demonstrates that CYP2D6 polymorphisms appeared to influence the disposition of lovastatin lactone in these subjects.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Yin OQ,Mak VW,Hu M,Fok BS,Chow MS,Tomlinson Bdoi
10.1007/s00228-011-1202-5subject
Has Abstractpub_date
2012-06-01 00:00:00pages
943-9issue
6eissn
0031-6970issn
1432-1041journal_volume
68pub_type
杂志文章abstract：OBJECTIVE:The aim of the present study was to investigate and characterise adverse drug reactions (ADRs) to drugs used in France for orthostatic hypotension (OH). METHODS:In this prospective and systematic study, 121 consecutive out-patients suffering from primary (Parkinson's disease, pure autonomic failure, multiple...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-005-0941-6
更新日期：2005-07-01 00:00:00
abstract：OBJECTIVE:To test whether treatment with fenofibrate decreases asymmetric dimethylarginine (ADMA) level in hypertriglyceridemic individuals. METHODS:In the present study, 45 subjects with hypertriglyceridemia were recruited to receive treatment with fenofibrate (200 mg/d). Serum concentrations of ADMA, malondialdehyde...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-005-0095-6
更新日期：2006-03-01 00:00:00
abstract：:Three groups of patients with biliary tract disease treated by cholecystectomy were given ceftriaxone. In Group 1 single doses of 150 mg and 1500 mg were given on Days 1 and 5 after cholecystectomy. In Group 2 2 g was given daily for 6 days and the cholecystectomy was on Day 2. Patients in Group 3 received 2 g every 1...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00607958
更新日期：1986-01-01 00:00:00
abstract：OBJECTIVES:To compare 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) as substrates for the methylation reaction catalysed by the enzyme thiopurine S-methyltransferase (TPMT). METHODS:TPMT activity in haemolysed red blood cells of healthy blood donors was determined twice, using the same experimental setting and equa...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280000137
更新日期：2000-07-01 00:00:00
abstract：:Caffeine metabolites in urine from premature infants were analysed by TLC and HPLC. Caffeine, dimethyluric acids, mono- and dimethylxanthines and, for the first time, a uracil derivative (6-amino-5-[N-methylformylamino]-1,3-dimethyluracil) were identified. ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00613531
更新日期：1986-01-01 00:00:00
abstract：OBJECTIVES:To explore the views and perspectives of children on the unlicensed/off-label use of medicines in children and on the participation of children in clinical trials. METHODS:Focus-group discussions, involving school children, were carried out in a range of primary and secondary schools in Northern Ireland. A ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-011-1110-8
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：OBJECTIVE:We sought to quantify the influence of the CYP3A inhibitor erythromycin on the pharmacokinetics of everolimus, a CYP3A substrate. METHODS:This was a two-period, single-sequence, crossover study in 16 healthy subjects. In period 1, subjects received the reference treatment of a single 2-mg dose of everolimus....
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-004-0866-5
更新日期：2005-03-01 00:00:00
abstract：:The metabolic fate and ACTH-suppressant activity of two injectable dexamethasone esters, 21-phosphate and 21-sulphate, were studied in healthy men. After i.v. injection of 20mg free steroid alcohol, dexamethasone phosphate was efficiently hydrolyzed to free dexamethasone, reaching its peak plasma concentration within ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00618778
更新日期：1981-01-01 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：PURPOSE:The survival of esophageal and gastric cancer patients treated with chemotherapy is rarely assessed outside of clinical trials. Therefore, we compared the effectiveness of various curative or palliative chemotherapy regimens on the survival of esophageal and gastric cancer patients in a "real world" clinical se...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-02883-3
更新日期：2020-07-01 00:00:00
abstract：:Nicotine chewing gum (Nicorette 4 mg) and an identical placebo gum were administered on different days, in a double-blind cross over fashion, to 4 men, aged 25-52 years, and 4 women, aged 21-49 years, all healthy non-smokers. The subjects chewed the gum for 30 min and heart rate, blood pressure, electrocardiogram, fin...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00613610
更新日期：1982-10-01 00:00:00
abstract：OBJECTIVES:Evidence exists to suggest that diclofenac is metabolised by CYP2C9. The present study was undertaken in order to evaluate the effect of the single CYP2C9*3 variant on drug metabolism using diclofenac as a probe drug. METHODS:A single dose of diclofenac was administered orally to 12 healthy subjects in whom...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050722
更新日期：2000-04-01 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：:The plasma kinetics of timolol administered orally and intravenously to 5 male subjects were examined. Bioavailability was reduced by 25% when the drug was taken orally. Mean plasma half-life after oral dosing was 4.86 h, and after intravenous administration it was 4.56 h; the difference was not significant. The volum...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00716385
更新日期：1978-12-18 00:00:00
abstract：:The efficacy and safety of almitrine bismesylate, a new respiratory stimulant, in patients with the hypoxaemic form of chronic respiratory insufficiency caused by chronic bronchitis and emphysema has been assessed. The multicentre trial of 12 weeks duration was double-blind and placebo controlled, with individual and ...
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/BF00315025
更新日期：1990-01-01 00:00:00
abstract：AIMS:The study aimed to identify and describe adverse drug reactions and adherence to clinical guidelines in patients receiving treatment for type 2 diabetes mellitus (T2DM) in Cameroon. METHODS:The method used was a cross-sectional study at a tertiary diabetes care service in Yaoundé, Cameroon. Adult T2DM patients at...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-02949-2
更新日期：2020-11-01 00:00:00
abstract：:We have previously shown that inhaled salbutamol further increases the bronchodilator response after the maximum effect of theophylline has been obtained in patients with severe chronic bronchitis. We now report the results of adding maximally effective doses of theophylline to the maximum response obtainable from sal...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542540
更新日期：1982-01-01 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
abstract：PURPOSE:Lithium (Li), the first-line treatment of bipolar disorder, was first developed as an immediate-release form with a routine therapeutic drug monitoring 12 h after the last dose. In Europe, the most commonly prescribed form is a sustained release (srLi). Yet no pharmacokinetics (PK) study has been published of s...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-018-2605-3
更新日期：2019-04-01 00:00:00
abstract：BACKGROUND:Serious adverse effects have been observed with some non-sedative H1-antihistamines (terfenadine and astemizole) when they were associated with drugs known to inhibit their metabolism. However, this is not a class effect, and this interaction should be considered on a case-by-case basis. The aim of this stud...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-005-0917-6
更新日期：2005-06-01 00:00:00
abstract：OBJECTIVE:We investigated the frequencies of the functionally important variants of the CYP2A6 gene in black African populations. METHODS:Using genomic DNA sequencing, polymerase chain reaction (PCR)-restriction fragment length polymorphism and allele-specific PCR, the allele frequencies of CYP2A6 *1A, *1B, *2, *4A, *...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-004-0854-9
更新日期：2005-02-01 00:00:00
abstract：:Plasma levels of canrenone and 'total metabolites' after base hydrolysis were compared in young and elderly subjects following single and multiple doses of spironolactone. After the initial dose on Day 1, plasma levels of canrenone and 'total metabolites' were higher in the young than in the elderly group, and signifi...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00549591
更新日期：1984-01-01 00:00:00
abstract：OBJECTIVE:Psychotropic drug use among nursing home residents with regard to diagnostic indications and patient- and institution characteristics was analysed. METHODS:A cross-sectional study of medication data from 1552 residents at 23 nursing homes in Bergen, Norway, was performed. Psychotropic drug use (neuroleptics,...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280100348
更新日期：2001-09-01 00:00:00
abstract：PURPOSE:Tamsulosin is one of the most potent drugs currently available to treat benign prostatic hyperplasia. Cytochrome P450 (CYP) 2D6 and CYP3A are the two major enzymes responsible for tamsulosin metabolism. The purpose of this study was to evaluate the effects of CYP2D6 and CYP3A5 genetic polymorphisms on the pharm...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-018-2501-x
更新日期：2018-10-01 00:00:00
abstract：:Blood levels of racemic chloroquine and its main metabolites desethylchloroquine and bisdesethylchloroquine were measured in 29 patients treated chronically for rheumatoid arthritis. In six patients, the concentrations were followed during a one day dosage interval. There was considerable intersubject variability in t...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00280130
更新日期：1992-01-01 00:00:00
abstract：OBJECTIVE:Gentamicin population pharmacokinetics in newborns were studied with special reference to possible gender effects. METHODS:Steady-state serum levels ( n=139) were obtained from 79 neonates with a mean birth weight of 2.1 kg, mean gestational age of 35.1 weeks and mean age at the time of sampling of 4.2 days....
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-003-0663-6
更新日期：2003-12-01 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：:The effects of single oral doses of mequitazine (5 and 10 mg), terfenadine (60 mg) and triprolidine (10 mg) as active controls, and placebo were evaluated on visuo-motor coordination, digit symbol substitution, critical flicker fusion and dynamic visual acuity, and on subjective assessments of mood and well-being in s...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542129
更新日期：1983-01-01 00:00:00
abstract：:In 12 patients undergoing coloscopy, 0.5 mg digoxin in aqueous alcoholic solution was injected into the transverse colon. The late maximum of the blood level curve at about 2 hours after the administration suggested delayed absorption of the glycoside. However, the 24 hour urinary excretion of 17 +/- 3.4% in 8 patient...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00614003
更新日期：1975-12-19 00:00:00
