Abstract:
OBJECTIVE:Theophylline is metabolized to 1,3-dimethyluric acid (1,3-DMU), 3-methylxanthine, and 1-methylxanthine by CYP1A2 and partly by CYP2E1. Because 1,3-DMU is the major metabolite of theophylline, the 1,3-DMU/theophylline ratio is viewed as a good indicator of theophylline metabolic clearance. Here, we investigated the associations between 1,3-DMU/theophylline ratios and genetic polymorphisms of CYP2E1 and CYP1A2. METHODS:Polymerase chain reaction (PCR) and direct sequencing or PCR-restriction fragment length polymorphism (RFLP) were performed to analyze CYP2E1 and CYP1A2 promoter polymorphisms in 62 Korean asthma patients. Plasma theophylline and 1,3-DMU levels were measured by liquid chromatography-tandem mass spectrometry. RESULTS:Eleven polymorphisms including Ins(96), -1566 T>A, -1515 T>G, -1414 C>T, -1295 G>C, -1055 C>T, -1027 T>C, -930 A>G, -807 T>C, -352 A>G, and -333 T>A were detected in the 5' flanking region of the CYP2E1 gene (numbering according to GenBank Accession number NT_017795). Of these, five single nucleotide polymorphisms (SNPs) (-1566 T>A, -1295 G>C, -1055 C>T, -1027 T>C, and -807 T>C) were closely linked. Another three polymorphisms (Ins(96,) -930 A>G, and -352 A>G) and two polymorphisms (-1515 T>G and -333 T>A) were also closely linked. The five closely linked polymorphisms were associated with significantly different 1,3-DMU/theophylline ratios between heterozygotes plus homozygotes of a rare allele (n=23, 0.0368+/-0.0171) and common allelic homozygotes (n=39, 0.0533+/-0.0343) (p=0.024 by Mann-Whitney U test). In the CYP1A2 gene, the -2964G>A polymorphisms exhibited a significant difference in 1,3-DMU/theophylline levels between heterozygotes plus homozygotes of a rare allele (n=30, 0.0406+/-0.0272) and homozygotes of a common allele (n=32, 0.0534+/-0.0316) (p=0.032). CONCLUSION:We confirm that hydroxylation at the 8 position of theophylline (1,3-DMU) is significantly affected by genetic polymorphism in CYP2E1 in addition to CYP1A2.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Yoon Y,Park HD,Park KU,Kim JQ,Chang YS,Song Jdoi
10.1007/s00228-006-0165-4subject
Has Abstractpub_date
2006-08-01 00:00:00pages
627-31issue
8eissn
0031-6970issn
1432-1041journal_volume
62pub_type
临床试验,杂志文章abstract::We have studied the pharmacokinetics of fluconazole in five patients on long-term haemodialysis. The single-pass extraction rate of the dialyzer was 59 (3.5)% (n = 4), and the serum concentration was reduced by haemodialysis for 3 or 4 h by 26 (3.2)% (n = 5) and 39 (2.2)% (n = 9) respectively. The estimated amount ext...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00265934
更新日期:1992-01-01 00:00:00
abstract:OBJECTIVES:Administration of fluvoxamine (FLV) with concomitant benzodiazepines is common in clinical situations. We studied the effects of the coadministration of FLV on plasma concentrations of alprazolam (ALP). We also studied the effects of CYP2C19(*)2 or CYP2C19(*)3 on these drug interactions. METHODS:The subject...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-003-0563-9
更新日期:2003-04-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to evaluate the pharmacokinetics of vancomycin in patients with severe acute pancreatitis (SAP). METHODS:Sixty-seven patients with SAP were included. The FPIA method was used to measure vancomycin serum trough concentrations, and the pharmacokinetic parameters were calculated using ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-016-2018-0
更新日期:2016-06-01 00:00:00
abstract::The antihypertensive effect of labetalol (L) was compared with that of clonidine (C) in a randomized cross-over study in 17 hypertensive outpatients on bendrofluazide (B). After treatment for two weeks with B(5 mg qd), either L (100 mg tid) or C (0.1 mg tid) was given and their doses were titrated at 2-weekly visits u...
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/BF00542319
更新日期:1982-01-01 00:00:00
abstract::In a double blind, randomised trial, the effects of 1 g aspirin and 1 g paracetamol were compared on bleeding time and platelet aggregation in 40 volunteers (20 females). Also investigated was the relationship between plasma aspirin esterase activity and both bleeding time and platelet aggregation after aspirin. Follo...
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/BF00543486
更新日期:1984-01-01 00:00:00
abstract::In seeking the putative mechanism of action of diethyldithiocarbamate (DTC) on the immune status of HIV infected patients, the plasma membrane fluidity of peripheral blood lymphocytes (PBL) from DTC-treated and untreated patients (CDC III-IVc1) was determined. Anisotropy values of the fluorescent probe 6-(9-anthroylox...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558135
更新日期:1989-01-01 00:00:00
abstract:OBJECTIVE:To evaluate the impact of the two most common CYP2C9 variant alleles (*2 and *3) on the maintenance dose of warfarin and on the quality of anticoagulation control in Brazilians. METHODS:Patients (n = 103) initiated warfarin therapy with 5 mg/day (or 2.5 mg/day when over 80 years old). The international norma...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-007-0385-2
更新日期:2008-01-01 00:00:00
abstract::We have evaluated the effects of repaglinide, a new non-sulphonylurea oral hypoglycaemic agent that has a stimulatory effect on insulin secretion. Forty-four patients with NIDDM, already treated with a sulphonylurea, took part in an open, randomised, group comparison study of 12 weeks duration, during which they recei...
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/BF00315490
更新日期:1993-01-01 00:00:00
abstract:OBJECTIVES:Inhaled corticosteroids (ICS) are widely used in the treatment of asthma. We studied the suspected adverse drug reactions (sADRs) reported during the use of ICS in the Netherlands. METHODS:In the Netherlands, health professionals and patients can report suspected ADRs to the Pharmacovigilance Centre Lareb. ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-006-0102-6
更新日期:2006-05-01 00:00:00
abstract:OBJECTIVES:A temporal relationship between the increasing use of antibiotics and the increasing levels of antibiotic resistance has been established for Streptococcus pneumoniae. There are also data that support the presence of a geographic correlation between the level of resistance and the pattern of use among differ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-003-0724-x
更新日期:2004-04-01 00:00:00
abstract::In eight patients with uncomplicated non insulin dependent diabetes mellitus, serum insulin levels, serum C-peptide levels and blood glucose levels were measured before and after oral administration of glibenclamide 0.1 mg/kg body weight and a test meal, or after a test meal alone. The rise in serum insulin levels per...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00265847
更新日期:1991-01-01 00:00:00
abstract:BACKGROUND:Maintenance of the structural and functional integrity of the skeleton is a critical function of a continuous remodeling driven by highly associated processes of bone resorption and synthetic activities driven by osteoclasts and osteoblasts, respectively. Acceleration of bone turnover, accompanied with a dis...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-006-0174-3
更新日期:2006-10-01 00:00:00
abstract::To evaluate the possible effect of quinidine on digoxin bioavailability, the steady state digoxin kinetics was examined with and without concomitant quinidine therapy, in 7 cardiac patients after simultaneous administration of oral digoxin and intravenous [3H]-digoxin. In the presence of quinidine, the absorption rate...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00613925
更新日期:1983-01-01 00:00:00
abstract::Tolbutamide (1 g/70 kg) was administered as a single intravenous dose to 31 healthy, non-smoking, drug-free males between 23 and 87 years old and the total amounts of hydroxy and carboxytolbutamide excreted in 24 h were measured. There was a significant decrease in the urinary recovery of both metabolites with age. Th...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF02336696
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine wh...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-015-1934-8
更新日期:2015-12-01 00:00:00
abstract::The metabolism of hydralazine in a group of slow acetylator patients with the drug-induced lupus syndrome was compared with the metabolism in asymptomatic control subjects. There were no toxicologically significant difference in metabolite excretion between the groups which reached statistical significance, although t...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00556891
更新日期:1984-01-01 00:00:00
abstract::We have studied the pharmacokinetics of tulobuterol given transdermally or by aerosol inhalation in healthy male volunteers. Tulobuterol was rapidly absorbed after inhalation, with a tmax of 0.8-1.5 h. The Cmax and the AUC increased linearly with dose. Tulobuterol was well absorbed after transdermal administration, wi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00316473
更新日期:1993-01-01 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: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::A randomised, placebo controlled clinical trial was conducted to examine the efficacy of a homeopathic after-bite gel in the symptomatic relief of mosquito bites. Sixty eight healthy volunteers were bitten under laboratory conditions by Aedes aegypti mosquitoes at three spots, on the ventral aspect of the forearm. One...
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/BF00192367
更新日期:1995-01-01 00:00:00
abstract:OBJECTIVE:To study the effect of cisplatin on plasma concentrations and urinary excretion of carnitine in ten patients with different malignancies treated with chemotherapy. METHODS:Carnitine concentrations were determined using a radioenzymatic assay and other metabolites by routine methods of clinical chemistry. Ren...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002280050504
更新日期:1998-09-01 00:00:00
abstract:PURPOSE:To investigate the impact of valproic acid (VPA) and genetic polymorphism of the major metabolizing enzyme (UGT1A4, UGT2B7) of lamotrigine (LTG) and VPA on LTG concentration in Chinese epileptic children. METHODS:Three single nucleotide polymorphisms (UGT1A4*3, UGT2B7 -161C > T and UGT2B7*2) were analyzed by p...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-015-1925-9
更新日期:2015-11-01 00:00:00
abstract::The antihypertensive effect of a new vasodilator with betablocking properties (SK & F 92657) was investigated in 10 patients with mild to moderate essential hypertension. After a mean treatment period of 26,5 weeks (6,5-49 weeks) blood pressure was significantly reduced, from 168 +/- 22/106 +/- 6 mmHg to 144 +/- 19/94...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00605990
更新日期:1982-01-01 00:00:00
abstract::The pharmacokinetics of the new lipid-lowering drug bezafibrate has been investigated in patients with impaired renal function and hyperlipoproteinaemia. 12 patients received a single oral dose of bezafibrate 300 mg. Plasma and urine samples were collected and bezafibrate was analyzed by gas chromatography. Eight of t...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00627922
更新日期:1981-01-01 00:00:00
abstract:PURPOSE:The purpose of the present study was to examine the relationship between the incidence of hyperammonemia and changes in the prescribing of concomitant antiepileptic drugs (AEDs) in patients receiving valproic acid. METHODS:We evaluated 40,363 plasma samples from 6009 epilepsy patients obtained from 2006 to 201...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1939-3
更新日期:2015-12-01 00:00:00
abstract::The immunosuppressive activity of azathioprine (AZA) is unpredictable and depends on the formation of intracellular thiopurine ribonucleotides. However, the quantification of these active thiopurines presents difficult analytical problems. It has recently been postulated that plasma concentrations of 6-thiouric acid (...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558158
更新日期:1989-01-01 00:00:00
abstract::In patients requiring a high or low dose of theophylline the pharmacokinetics of theophylline and enprofylline were studied. The low-dose group took an average daily dose of 8.91 mg/kg body wt. and the high-dose group 24.75 mg/kg body wt. The average half-life of theophylline in the former was 7.11 h and in the latter...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00547379
更新日期:1985-01-01 00:00:00
abstract::A new device for IV admixtures has been developed in Israel, the Vialink minibag. It consists of a partly filled minibag, attached by rubber tubing to a sterile receptable into which various types of vials containing drugs can be firmly inserted. Time and motion studies were conducted to determine the time and cost as...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00194973
更新日期:1994-01-01 00:00:00
abstract::Amitriptyline has clinically important interactions with ethanol. Five healthy volunteers received 25 mg of amitriptyline orally, preceded by one hour and followed for eight hours by oral ethanol (or juice), dosed to achieve and maintain blood ethanol concentrations of 800 mg/l. In the presence of ethanol, amitriptyli...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF01037943
更新日期:1983-01-01 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