Abstract:
:1. Studies using human liver microsomes and six recombinant human CYP isoforms (i.e. CYP1A2, 2A6, 2B6, 2D6, 2E1 and 3A4) were performed to identify the cytochrome P450 (CYP) isoform(s) involved in the ring 4-hydroxylation and side-chain N-desisopropylation of propranolol enantiomers in humans. 2. alpha-Naphthoflavone and 7-ethoxyresorufin (selective inhibitors of CYP1A1/2) inhibited the N-desisopropylation of R- and S-propranolol by human liver microsomes by 20 and 40%, respectively, while quinidine (a selective inhibitor of CYP2D6) abolished the 4-hydroxylation of both propranolol enantiomers almost completely. In contrast, sulphaphenazole (CYP2C8/9 inhibitor), S-mephenytoin (CYP2C19 inhibitor), troleandomycin (CYP3A3/4 inhibitor) and diethyldithiocarbamate (CYP2E1 inhibitor) elicited only weak inhibitory effects on propranolol metabolism via the two measured metabolic pathways. 3. Significant (P < 0.01) correlations were observed between the microsomal N-desisopropylation of both propranolol enantiomers and that for the O-deethylation of phenacetin among the 11 different human liver microsome samples (r = 0.98 and 0.77 for R- and S-propranolol, respectively). A marginally significant (r = 0.60, P congruent to 0.05) correlation was also observed between N-desisopropylation of S-, but not of R-propranolol and the 4'-hydroxylation of S-mephenytoin. No significant correlations were observed between the N-desisopropylation of propranolol enantiomers and the 2-hydroxylation of desipramine, the hydroxylation of tolbutamide or the 6 beta-hydroxylation of testosterone. 4. Significant (P < 0.01) correlations were observed between the microsomal 4-hydroxylation of R- and S-propranolol and the 2-hydroxylation of desipramine (r = 0.85 and 0.98, respectively). A weak (r = 0.66), albeit significant (P < 0.05) correlation was observed between the 4-hydroxylation of R-, but not of S-propranolol and the hydroxylation of tolbutamide. No significant correlations were observed between the 4-hydroxylation of propranolol enantiomers and the oxidation of other substrates for CYP1A2, 2C19, and 3A3/4. 5. Recombinant human CYP1A2 and CYP2D6 exhibited comparable catalytic activity with respect to the N-desisopropylation of both propranolol enantiomers; only expressed CYP2D6 exhibited a marked catalytic activity with respect to the 4-hydroxylation of both propranolol enantiomers.(ABSTRACT TRUNCATED AT 400 WORDS)
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Yoshimoto K,Echizen H,Chiba K,Tani M,Ishizaki Tdoi
10.1111/j.1365-2125.1995.tb04472.xsubject
Has Abstractpub_date
1995-04-01 00:00:00pages
421-31issue
4eissn
0306-5251issn
1365-2125journal_volume
39pub_type
杂志文章abstract::1. The elimination of antipyrine was investigated before and after intravenous administration of haem arginate (3 mg haem kg-1 day-1 on three or four successive days) to six patients with variegate porphyria in remission. 2. Haem arginate decreased the faecal content of protoporphyrin from 557 +/- 91 to 118 +/- 32 (me...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb05315.x
更新日期:1988-12-01 00:00:00
abstract::The excretion of diazepam, N-desmethyldiazepam, temazepam and oxazepam in breast milk was studied during withdrawal of a 22-year-old patient from combined high dose diazepam and oxazepam therapy. Concentrations of these benzodiazepines in plasma from both the woman and her nursing infant (1 year old) were also documen...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb03612.x
更新日期:1990-01-01 00:00:00
abstract::Regulatory science underpins the objective evaluation of medicinal products. It is therefore imperative that regulatory science and expertise remain at the cutting edge so that innovations of ever-increasing complexity are translated safely and swiftly into effective, high-quality therapies. We undertook a comprehensi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14099
更新日期:2020-12-01 00:00:00
abstract::1 Benzodiazepines are regarded as pure anxiolytics, and their value in the treatment of depression is controversial. Nevertheless, symptoms of anxiety and depression coexist in patients with endogenous or neurotic depression, and clinical trials indicate that depressed patients respond better to a benzodiazepine-tricy...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1981.tb01835.x
更新日期:1981-01-01 00:00:00
abstract:AIM:Drug-induced liver injury (DILI) is often responsible for acute liver failure, drug withdrawal, boxed warnings or drug non-approval. Therefore, we conducted a case-control study to determine the hepatotoxic risk of a wide range of drugs. METHODS:The Berlin Case-Control Surveillance Study FAKOS included all 51 Berl...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12565
更新日期:2015-06-01 00:00:00
abstract:AIMS:To examine the effects of salbutamol and L-arginine, two compounds acting largely on the endothelium, and the endothelium-independent agent nitroglycerin on blood pressure, arterial compliance, cardiac function and vascular resistance. METHODS:Continuous radial pulse wave analysis, whole-body impedance cardiograp...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2009.03434.x
更新日期:2009-07-01 00:00:00
abstract:AIMS:We aimed to examine the frequency of high-dose (defined as mean chlorpromazine mg equivalent doses above 1000) antipsychotic prescriptions in schizophrenia and their clinical correlates in the context of a comparison between studies in 2001 and 2004 within six East Asian countries and territories. METHODS:Prescri...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2125.2008.03304.x
更新日期:2009-01-01 00:00:00
abstract::Adverse drug reactions come at a considerable cost on society. Social media are a potentially invaluable reservoir of information for pharmacovigilance, yet their true value remains to be fully understood. In order to realize the benefits social media holds, a number of technical, regulatory and ethical challenges rem...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12717
更新日期:2015-10-01 00:00:00
abstract:AIM:To investigate the effect of the P-glycoprotein inhibitor verapamil on the pharmacokinetics and pharmacodynamics of dabigatran etexilate (DE). METHOD:In this two part multiple crossover trial in 40 healthy subjects, DE 150 mg was given alone or with verapamil at different doses, duration of treatment (single vs. m...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2012.04453.x
更新日期:2013-04-01 00:00:00
abstract:AIMS:BG00010 is a protein in the glial cell line-derived neurotrophic factor (GDNF) family. It is a selective ligand for the GDNF family receptor alpha-3 (GFRα3) co-receptor that normalizes cellular changes resulting from damage or disease, and potentially alleviates neuropathic pain. The main objectives of this study ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.12941
更新日期:2016-07-01 00:00:00
abstract::1 Infusion of isoprenaline into dorsal hand veins preconstricted with noradrenaline produced vasodilatation in four subjects out of five which was reversed by addition of propranolol. It is confirmed that beta-adrenoceptors are present in the hand veins of most subjects. 2 Addition of either propranolol or practolol t...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1975.tb01564.x
更新日期:1975-04-01 00:00:00
abstract::1. We have utilised a new non-imaging echo-Doppler cardiac output device, using the principle of attenuated compensated volume flow (ACVF), to assess the cardiovascular effects of atenolol and buccal nitroglycerin (NTG) in a placebo-controlled study of 30 patients with coronary disease. 2. Atenolol (4 mg i.v.) reduced...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1990.tb03696.x
更新日期:1990-06-01 00:00:00
abstract:AIMS:We investigated the effect of angiotensin converting enzyme inhibitors (ACEIs) on postsynaptic adrenoceptor sensitivity and compared the effect of the lipophilic ACEI, quinapril, and that of hydrophilic agent, enalapril in human vessels. METHODS:Alpha-adrenoceptor sensitivity was evaluated using the dorsal hand v...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2125.1998.00834.x
更新日期:1998-12-01 00:00:00
abstract:AIMS:Spirometry, plethysmography and impulse oscillometry (IOS) measure different aspects of lung function. These methods have not been compared for their ability to assess long- and short-acting anticholinergic agents. We therefore performed a double-blind, placebo-controlled, four-way cross-over study in 30 healthy s...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2006.02594.x
更新日期:2006-04-01 00:00:00
abstract:AIMS:To investigate the extent of dose-related off-label antibiotic paediatric prescribing in primary care and to identify any potential clinical effects, particularly of lower than recommended dose prescribing. METHODS:Assessment of antibiotic prescribing in 168 396 children aged 0-16 years for the year 1999-2000 fro...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2003.01835.x
更新日期:2003-07-01 00:00:00
abstract::1 The effects of age and sex on the disposition of clobazam (CBZ), a 1.5-benzodiazepine derivative, were evaluated in a series of 29 healthy volunteers aged 18 to 72 years, who ingested single 20 mg oral doses. CBZ kinetics were determined from multiple plasma concentrations measured during 7 days after the dose. 2 CB...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1981.tb01281.x
更新日期:1981-11-01 00:00:00
abstract::1 Cimetidine has been reported to reduce serum calcium and parathyroid hormone (PTH) levels in primary hyperparathyroidism, but some studies have reported negative findings. 2 A double-blind, controlled trial of cimetidine in this condition was, therefore, conducted. Eight patients were given cimetidine and placebo fo...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1982.tb04960.x
更新日期:1982-11-01 00:00:00
abstract:AIMS:Using human liver microsomes from donors of the CYP2D6 poor and extensive metabolizer genotypes, the role of individual cytochromes P-450 in the oxidative metabolism of dihydrocodeine was investigated. METHODS:The kinetics of formation of N- and O-demethylated metabolites, nordihydrocodeine and dihydromorphine, w...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.1997.t01-1-00626.x
更新日期:1997-12-01 00:00:00
abstract::Six patients received 10 mg of midazolam intravenously during the anhepatic period of liver transplantation. Arterial blood was sampled during this time and for a similar period following revascularisation. The plasma was analysed using gas chromatography and electron capture detection (GC-ECD) for midazolam alpha-hyd...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1989.tb03429.x
更新日期:1989-05-01 00:00:00
abstract:AIMS:In vitro data indicate that imipramine (IMI), a widely used tricyclic antidepressant drug, is N-demethylated by several isoforms of cytochrome P450, which include CYP3A4. The aim of this study was to investigate the role of CYP3A in the in vivo N-demethylation of IMI. METHODS:Healthy subjects were given troleando...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2125.1997.00649.x
更新日期:1997-08-01 00:00:00
abstract::1 The protein binding of seven non-steroidal anti-inflammatory drugs (indomethacin, tolmetin, salicylic acid, ibuprofen, flurbiprofen, naproxen and GP53,633) and warfarin was investigated by equilibrium dialysis in simultaneous samples of synovial fluid and plasma from 12 arthritic patients. 2 The protein binding of a...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb01469.x
更新日期:1983-01-01 00:00:00
abstract::1. The pharmacokinetics and pharmacodynamics of a single dose of trandolapril, an angiotensin converting enzyme (ACE) inhibitor with an active metabolite, trandolaprilat, which is in part further metabolised prior to renal elimination, were evaluated in 31 subjects with a wide range of renal function (creatinine clear...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract::Little is known about the administration of direct-acting oral anticoagulants (DOACs) and the occurrence of alopecia. Our aim was to analyse the reports of alopecia following DOAC administration received until 2 May 2018 from VigiBase, the World Health Organization database. A descriptive analysis of age, sex, serious...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14221
更新日期:2020-08-01 00:00:00
abstract::1. Recently, some cases have been reported where intravenous use of omeprazole was followed by loss of vision. We followed up a cohort of close to 140,000 persons during periods of treatment and non-treatment with five anti-ulcer drugs. 2. The relative risk of vascular disorders of the eye during use of omeprazole com...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.1996.40211.x
更新日期:1996-08-01 00:00:00
abstract:AIMS:To compare gastric acid suppression by netazepide, a gastrin/CCK2 receptor antagonist, with that by a proton pump inhibitor (PPI), and to determine if netazepide can prevent the trophic effects of PPI-induced hypergastrinaemia. METHODS:Thirty healthy subjects completed a double-blind, randomized, parallel group t...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.12534
更新日期:2015-05-01 00:00:00
abstract::1. The inhibitory effect of sufotidine, a new histamine H2-receptor antagonist, on gastric secretion of acid and pepsin was studied in six healthy male volunteers. This was a three-way, cross-over, randomized, double-blind study. On each of 3 study days, the drug in a dose of 600 mg, or placebo, was administered eithe...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1989.tb03519.x
更新日期:1989-10-01 00:00:00
abstract::In order to elucidate the mechanisms by which beta-adrenoceptor blockade leads to a reduction in portal pressure, we have measured portal pressure, heart rate and cardiac index in 17 patients with cirrhosis and portal hypertension following the oral administration of the selective beta 2-adrenoceptor blocking agent, I...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02413.x
更新日期:1984-06-01 00:00:00
abstract::The airway and cardiovascular effects of intravenous neurokinin A (NKA) and substance P (SP) were compared in six normal subjects. Both SP and NKA increased skin temperature (SkT) and heart rate (HR), but SP was more potent than NKA by factors of 6 and 20 respectively. No change in systolic blood pressure (BP) occurre...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1988.tb03302.x
更新日期:1988-02-01 00:00:00
abstract:AIMS:In man a neurokinin-1 (NK1) receptor antagonist has previously been shown to be ineffective in the prevention of motion-induced nausea. The antiemetic efficacy of NK1 receptor antagonists against chemotherapy-induced emesis is, however, enhanced when combined with a 5-HT3 receptor antagonist. Hence the efficacy of...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2125.2000.00221.x
更新日期:2000-07-01 00:00:00
abstract::1. The absorption of ciprofloxacin from different regions of the human gastrointestinal tract was investigated in four healthy males using a remote-controlled drug delivery device (hf-capsule). 2. Significant differences in AUC were observed in the control study (oral administration of ciprofloxacin solution without t...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb03740.x
更新日期:1990-07-01 00:00:00