Abstract：
:1 The disposition in urine of debrisoquine and its hydroxylated metabolites has been studied in subjects of the 'extensive metabolizer' (EM; n = 5) and 'poor metabolizer' (PM; n = 5) phenotypes. The 4-hydroxylation of debrisoquine by PM subjects following a 10 mg oral dose was capacity-limited and displayed significant dose-dependency over a range of 1-20 mg. In contrast, the EM subjects' ability to perform this metabolic oxidation did not deviate from first-order kinetics over a dose range of 10-40 mg. 2 The disposition of debrisoquine in plasma following a 10 mg oral dose has been studied in EM (n = 4) and PM (n = 3) subjects. Whilst PM subjects displayed significantly higher plasma levels of debrisoquine at all time points following 1 h post-dosing, and higher values for areas under the plasma concentration-time curve (EM: 105.6 +/- 7.0 ng ml-1 h; PM: 371.4 +/- 22.4 ng ml-1 h, 2P less than 0.0001), neither debrisoquine plasma half-life (EM: 3.0 +/- 0.5 h; PM: 3.3 +/- 0.4 h) nor renal clearance of the drug (EM: 152.8 +/- 30.3 ml min-1; PM: 137 +/- 4.5 ml min-1) displayed significant inter-phenotype differences. 3 The results of these investigations show that the phenotyping of individuals for debrisoquine oxidation status by means of a 'metabolic ratio' derived from a single 0-8 h urine sample has a sound kinetic basis. The kinetic differences between the two phenotypes would strongly suggest that the metabolic defect manifested in PM subjects is one of pre-systemic elimination capacity.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Sloan TP,Lancaster R,Shah RR,Idle JR,Smith RLdoi
10.1111/j.1365-2125.1983.tb01528.xsubject
Has Abstractpub_date
1983-04-01 00:00:00pages
443-50issue
4eissn
0306-5251issn
1365-2125journal_volume
15pub_type
杂志文章abstract：:1. Using human mononuclear leucocytes as target cells, we have investigated the bioactivation of dapsone (DDS) to a cytotoxic metabolite in the presence of microsomes from nine human livers. Values for NADPH dependent toxicity ranged from 8.8-27% (15.8 +/- 5.9%) and were similar to those for microsomes from control mi...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1989.tb03517.x
更新日期：1989-10-01 00:00:00
abstract：AIMS:To assess the age-associated changes over time of plasma paraxanthine/caffeine (PAX/CAF) ratios used as a probe for CYP1A2 activity. METHODS:Intraindividual and interindividual variabilities in PAX/CAF ratio were compared by phenotyping with caffeine, 16 young and 16 elderly healthy subjects on five occasions. R...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.0306-5251.2001.01494.x
更新日期：2001-11-01 00:00:00
abstract：AIMS:The objective of this study was to estimate the number of fractures attributed to oral corticosteroid use. METHODS:Information was obtained from the General Practice Research Database which contains medical records of general practitioners in the UK. The total number of corticosteroid-related fractures during a c...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.0306-5251.2001.1385.x
更新日期：2001-06-01 00:00:00
abstract：:Nine healthy male subjects received oral fluconazole 400 mg daily, ketoconazole 200 mg twice daily or no treatment for 6 days according to a randomized, cross-over design. A single 250 mg oral dose of phenytoin suspension was administered on day 5 and serum phenytoin concentrations were measured over the following 48 ...
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.1365-2125.1992.tb04111.x
更新日期：1992-07-01 00:00:00
abstract：AIMS:To assess the effect of the calcitonin gene-related peptide (CGRP) receptor antagonist, telcagepant, on the haemodynamic response to sublingual nitroglycerin (NTG). METHODS:Twenty-two healthy male volunteers participated in a randomized, placebo-controlled, double-blind, two-period, crossover study. Subjects rece...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1365-2125.2010.03869.x
更新日期：2011-05-01 00:00:00
abstract：AIM:To investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of the highly selective oral p38alpha/beta mitogen-activated protein (MAP) kinase inhibitor Org 48,775-0 in a first-in-human study. METHODS:In the single ascending dosing (SAD) study, an oral dose of Org 48,775-0 (0.3-600 mg) was evalua...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14655
更新日期：2020-11-17 00:00:00
abstract：:1 The effects of the thromboxane synthetase inhibitor dazoxiben (UK 37248) on haemodynamics, blood gases, thromboxane and prostacyclin release and on arrhythmias were examined in anaesthetised greyhounds subject to acute coronary artery occlusion and reperfusion. 2 Ten minutes after the administration of UK 37248 2 mg...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1983.tb02115.x
更新日期：1983-01-01 00:00:00
abstract：:In six healthy subjects a 250 g steak significantly increased the systemic clearance of indocyanine green. During a steady-state infusion of propranolol there was a rapid decrease (mean 35%) in blood propranolol concentrations within 5 min of feeding and levels were reduced for 30 min before gradually returning toward...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1983.tb01516.x
更新日期：1983-03-01 00:00:00
abstract：AIMS:The Transdermal Delivery System (TDS) is a liquid formulation that can be applied to the skin via a metered pump spray to deliver drug to the systemic circulation. The aims of this study were to assess the ability of the TDS preparation to deliver testosterone systemically, and to characterize the pharmacokinetic ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1365-2125.2005.02542.x
更新日期：2006-03-01 00:00:00
abstract：AIMS:In the Swiss heroin substitution trials, patients are treated with self-administered diacetylmorphine (heroin). Intravenous administration is not possible in patients that have venosclerosis. Earlier studies have demonstrated that oral diacetylmorphine may be used, although it is completely converted to morphine p...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2008.03286.x
更新日期：2008-12-01 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：:The current U.K. trial protocol (UKALL XI) for childhood lymphoblastic leukaemia demands mercaptopurine (MP) dose escalation in children who tolerate daily 75 mg/m2 MP (100% dose) without cytopenias. The previous trial (UKALL X) did not. MP metabolism was studied in a group of UKALL XI children (n = 21) who tolerated ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.1996.44921.x
更新日期：1996-10-01 00:00:00
abstract：:1. Meals empty more slowly when they contain fat. 2. This study investigated whether an intragastric fat preload in comparison with a water preload affected gastric emptying of a semisolid meal and antral motor activity, and whether cisapride reversed such effects. 3. Twelve healthy subjects were studied under three c...
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.tb05449.x
更新日期：1990-12-01 00:00:00
abstract：:1 The plasma levels of disopyramide and mono-N-dealkyldisopyramide were measured from 118 patients, and the protein binding of both drugs from 50 patients during chronic oral disopyramide therapy. 2 No significant correlation was seen between the daily dose of disopyramide and the achieved plasma drug concentration. 3...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1981.tb01134.x
更新日期：1981-04-01 00:00:00
abstract：:The disposition and effect of orally administered prazosin have been studied in eight women with hypertension which was uncontrolled by beta-adrenoceptor blockade during the last trimester of pregnancy. Results were compared with healthy men of similar age. The median time to peak concentration was 165 min during preg...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1983.tb02213.x
更新日期：1983-11-01 00:00:00
abstract：AIMS:Our study aimed to evaluate the impacts of the cytochrome P450 (CYP) 2B6-G516T and CYP2D6 genetic polymorphisms on pharmacokinetic and clinical parameters in patients receiving methadone maintenance treatment. METHODS:Opioid PhArmacoLogy (OPAL) was a clinical survey of the sociodemographic characteristics, histor...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1111/bcp.13936
更新日期：2019-07-01 00:00:00
abstract：:The concentration of chloroquine (CQ), dapsone (DDS) and pyrimethamine (PYR) in plasma and milk were measured following the coadministration of a single dose of chloroquine and Maloprim to lactating women. The milk to plasma area under the concentration-time curve (AUC) ratio ranged from 1.96 to 4.26 for CQ, 0.22 to 0...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1986.tb02967.x
更新日期：1986-12-01 00:00:00
abstract：:1. Preliminary results are reported from a long-term study aimed at recording the concentrations of serum lipids and lipoproteins at 6, 12 and 24 months of treatment with pindolol in young/middle-aged males with moderate hypertension. 2. Seventy-three patients have been recruited, of whom 47 have completed 6 months tr...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1987.tb03272.x
更新日期：1987-01-01 00:00:00
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 ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1995.tb04472.x
更新日期：1995-04-01 00:00:00
abstract：AIMS:The goal of this study was to determine the frequencies of important allelic variants in the TPMT, NAT2, GST, SULT1A1 and MDR-1 genes in the Egyptian population and compare them with the frequencies in other ethnic populations. METHODS:Genotyping was carried out in a total of 200 unrelated Egyptian subjects. TPMT...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2003.01786.x
更新日期：2003-06-01 00:00:00
abstract：:Plasma melatonin was used to determine overall beta-adrenergic transmission through pineal neuro-effector junctions during desmethylimipramine (DMI) treatment in 10 normal subjects. Changes in plasma melatonin indicated that an initial increase in noradrenaline (NA) transmission produced by DMI was counteracted by ada...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1985.tb02717.x
更新日期：1985-06-01 00:00:00
abstract：:1 We have performed a double-blind, randomized, 7-d cross-over study of the thromboxane synthetase inhibitor dazoxiben (UK 37248) in 20 patients with stable coronary heart disease. 2 All patients had a history of exertional angina of greater than two years duration and no patient had suffered a myocardial infarction i...
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.1365-2125.1983.tb02114.x
更新日期：1983-01-01 00:00:00
abstract：:1 Methimazole plasma concentrations were measured in two groups of hyperthyroid subjects after the oral administration of either carbimazole or methimazole. 2 With the HPLC method it was also possible to measure the concentration of a methimazole metabolite, 3-methyl-2-thiohydantoin in one patient. 3 Large interindivi...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1980.tb05823.x
更新日期：1980-02-01 00:00:00
abstract：:We have measured the psychological effects of acebutolol and atenolol in sixteen patients with essential hypertension. The drugs were administered in a randomized, placebo-controlled, double-blind manner, in single daily doses of 100 mg atenolol, 400 mg acebutolol or placebo for periods of 6 weeks, each drug period be...
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.1365-2125.1984.tb02356.x
更新日期：1984-03-01 00:00:00
abstract：:At a James Black Conference held in Oxford on 20-22 June 2011, a group of senior clinical pharmacologists and their junior colleagues, other medical specialists, and pharmacists discussed an agenda for UK clinical pharmacology for the next 5 years, addressing the following broad questions. How should UK clinical pharm...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2012.04233.x
更新日期：2012-06-01 00:00:00
abstract：:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The population pharmacokinetics and limited sampling strategies for ciclosporin monitoring have been extensively studied in renal and liver transplant recipients. Little is known about the pharmacokinetics of ciclosporin in patients undergoing haematopoietic allogeneic stem c...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2011.04116.x
更新日期：2012-04-01 00:00:00
abstract：:The oral delivery of peptides and proteins has been hampered by an array of obstacles. However, several promising novel oral delivery systems have been developed. This paper reviews the most advanced oral formulation technologies, and highlights key lessons and implications from studies undertaken to date with these o...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.12557
更新日期：2015-05-01 00:00:00
abstract：AIMS:Mexiletine has been reported to be hydroxylated by cytochrome P450 2D6 (CYP2D6) in humans. However, the involvement of CYP1A2 in the metabolism of mexiletine has been proposed based on the interaction with theophylline which is mainly metabolized by CYP1A2. The aim of this study was to clarify the role of human CY...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.1998.00048.x
更新日期：1998-07-01 00:00:00
abstract：:1 Mianserin does not affect the uptake of biogenic amines into rat brain, in contrast to tricyclic antidepressants which block amine uptake. 2 Mianserin increases the turnover of noradrenaline (NA) in rat brain after acute or chronic administration, whereas tricyclic antidepressants reduce turnover of NA and 5-hydroxy...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
abstract：:1. The objective of this study was to investigate the efficacy of home-medicated non-steroidal anti-inflammatory (NSAID) analgesics, using an electronic patient diary. Single doses of ketoprofen 25 mg and ketoprofen 50 mg were compared with ibuprofen 200 mg and placebo in the treatment of a single occasion of episodic...
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.1365-2125.1996.43613.x
更新日期：1996-10-01 00:00:00
