Abstract:
:The frequency distributions of the 0-8 h urinary metabolic ratios of debrisoquine and mephenytoin were measured in 111 healthy, unrelated Sinhalese resident in Sri Lanka. Blood samples were taken from 77 of these subjects for CYP2D6 genotyping. Bimodality in the distribution of the log10 debrisoquine/4-hydroxydebrisoquine ratio was not evident from visual inspection and by kernel density analysis. The results of genotyping indicated that 82% of the population were either homozygous for the wild-type CYP2D6 gene or heterozygous for the wild type allele and the whole gene deletion. Eighteen per cent of the Sinhalese population were heterozygous for the CYP2D6B mutation and the wild-type allele. All of these genotypes give rise to the extensive metaboliser phenotype in white Caucasians. No CYP2D6A mutations were identified and no individuals who were homozygous for the mutant alleles were detected, which is in accord with an absence of phenotypic poor metabolisers of debrisoquine. The mutant CYP2D6 allele frequency in Sinhalese (9%) is only half that observed in white Caucasians. The S/R-mephenytoin ratio ranged from 0.09 to 2.27 (median 0.38). By visual inspection and kernel density analysis the distribution of the S/R-mephenytoin ratio was bimodal and, using a value of 0.9 for the antimode, 16 (14%) subjects were poor metabolisers. In conclusion, the prevalence of the poor metaboliser phenotype in Sinhalese appears much lower for debrisoquine and higher for mephenytoin than in white Caucasians. These findings are similar to those observed in Indians living in Bombay and in Oriental populations.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Weerasuriya K,Jayakody RL,Smith CA,Wolf CR,Tucker GT,Lennard MSdoi
10.1111/j.1365-2125.1994.tb04384.xsubject
Has Abstractpub_date
1994-11-01 00:00:00pages
466-70issue
5eissn
0306-5251issn
1365-2125journal_volume
38pub_type
杂志文章abstract:AIMS:Various mathematical models have been developed to estimate glomerular filtration rate (GFR) incorporating variables such as age, gender, height, weight, serum creatinine, and body surface area (BSA). Because adjustments in drug dosing are often based on estimated values of renal function, it is important to defin...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.1997.t01-1-00567.x
更新日期:1997-09-01 00:00:00
abstract:AIMS:To establish whether the SCN1A IVS5-91 G > A polymorphism of the SCN1A gene, which encodes the neuronal sodium channel alpha subunit, affects responsiveness to the antiepileptic drugs (AEDS) carbamazepine and/or phenytoin. METHODS:SCN1A IVS5-91 G > A polymorphism was genotyped in 228 Japanese epileptic patients t...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2008.03203.x
更新日期:2008-08-01 00:00:00
abstract::1. A rapid intravenous bolus injection of 4.0 g Magnapen (which contains 2.0 g of ampicillin and 2.0 g of flucloxacillin) was to seven patients undergoing total hip replacement immediatly before induction of general anesthesia. Postoperatively the patients patients received 2.0 g Magnapen by intramuscular injection ev...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1978.tb00838.x
更新日期:1978-08-01 00:00:00
abstract::1 The clinical pharmacokinetics of the many benzodiazepines used to treat numerous and varied clinical conditions can be influenced by many factors. 2 Combinations of drugs efficacious in the central nervous system can change the onset, intensity and duration of effect as a result of pharmacological, physiological and...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1981.tb01843.x
更新日期:1981-01-01 00:00:00
abstract::1. The in vitro metabolism of omeprazole was studied in human liver microsomes in order to define the secondary metabolic pathways and identify the cytochrome P450 (CYP) isoforms responsible for the formation of the secondary metabolites of omeprazole. 2. The major secondary omeprazole metabolite was the hydroxysulpho...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1994.tb04310.x
更新日期:1994-06-01 00:00:00
abstract::Twenty-three elderly hypertensive subjects received nitrendipine 10mg daily by mouth for 8 days. Plasma nitrendipine concentrations were measured after the first and last dose. There was no significant difference in plasma concentrations at any time point between the two days nor in derived pharmacokinetic measurement...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb05283.x
更新日期:1988-09-01 00:00:00
abstract:AIMS:To assess safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of CNTO 7160, an anti-interleukin-33 receptor (IL-33R) monoclonal antibody, in healthy subjects and patients with asthma or atopic dermatitis (AD). METHODS:In Part 1 of this Phase I, randomized, double-blind, placebo-c...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14361
更新日期:2020-12-01 00:00:00
abstract::The binding of carbamazepine and carbamazepine 10,11-epoxide to serum, albumin and alpha 1-acid glycoprotein (AAG) was determined and compared at drug concentrations ranging from 0.5 to 400 mg/l using equilibrium dialysis and liquid chromatography. The total binding of carbamazepine in serum was determined primarily b...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02496.x
更新日期:1984-10-01 00:00:00
abstract:AIMS:To investigate the relationships between pretreatment folate concentrations, MTX pharmacokinetics and acute toxicities following high dose methotrexate (HD MTX) therapy. METHODS:MTX and its major extracellular metabolite 7-OH-MTX were measured in eight serum samples per HD MTX cycle in 65 consecutive osteosarcoma...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2011.04054.x
更新日期:2012-01-01 00:00:00
abstract::1. The effects of sodium octanoate and sodium salicylate on the rectal absorption of cefoxitin were investigated in healthy volunteers. Drug solutions were given either as a bolus or as a zero-order infusion. 2. On rectal infusion sodium octanoate and sodium salicylate both enhanced mean cefoxitin bioavailability (+/-...
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.tb05337.x
更新日期:1989-01-01 00:00:00
abstract::Widespread use of cocaine and its attendant toxicity has produced a wealth of benchwork studies and small animal investigations that evaluated the effects of cocaine on the cardiovascular system. Despite this wealth of knowledge, very little is known about the frequency or types of arrhythmias in patients with signifi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2010.03632.x
更新日期:2010-05-01 00:00:00
abstract::Ten patients with mild to moderate hypertension were treated for 9 weeks with a tablet formulation of pinacidil. Mean supine blood pressure fell from 174/100 to 148/84 mm Hg and mean supine pulse increased by 3 beats/min. Daily dosage was 40-100 mg, given in two or three divided doses. Plasma urea increased significan...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02456.x
更新日期:1984-08-01 00:00:00
abstract::1. Ototoxicity is a common and troublesome side-effect of high-dose aspirin treatment but there has been little previous study of the relationships between the degree of ototoxicity and the plasma concentrations of salicylate. 2. In order to investigate the relationships between aspirin dose, total and unbound plasma ...
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.tb03562.x
更新日期:1989-12-01 00:00:00
abstract::Osteoporosis is a skeletal disease characterized by a decrease in bone mass and bone quality that predispose an individual to an increased risk of fragility fractures. Evidence demonstrating a positive link between certain dietary patterns (e.g. Mediterranean diet or high consumption of fruits and vegetables) and bone...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12033
更新日期:2013-03-01 00:00:00
abstract::A method is described for the simultaneous determination of the carboxylic acid and N-acetyl-derivatives of primaquine, in plasma and urine. After oral administration of 45 mg primaquine, to five healthy volunteers, absorption was rapid, with peak primaquine levels of 153.3 +/- 23.5 ng/ml at 3 +/- 1 h, followed by an ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02369.x
更新日期:1984-04-01 00:00:00
abstract::In order to clarify the characteristics of absorption of 5-aminosalicylic acid (5-ASA) from the colon, a neutral solution was instilled into the right part of the colon and the rectum, respectively, in six volunteers. A laxative (bisacodyl) and liquid meals were given prior to each instillation. No significant differe...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb03301.x
更新日期:1988-02-01 00:00:00
abstract::A double-blind, placebo-controlled, cross-over trial of quinine in leg cramps occurring at rest was conducted in 22 elderly cramp sufferers. Despite demonstration of impaired quinine elimination in the elderly, prescription of the traditional dose of 300 mg quinine bisulphate at night failed to produce a significant (...
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.1365-2125.1987.tb03076.x
更新日期:1987-04-01 00:00:00
abstract:AIMS:It has been shown that the cellular uptake and cytotoxicity of anthracyclines decrease with increasing cell density in vitro, an event termed 'the inocculum effect'. It is not known whether such an effect occurs in vivo. In this study the relationships between white blood cell (WBC) count, plasma and cellular conc...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2010.03894.x
更新日期:2011-04-01 00:00:00
abstract::1 Minute ventilation, alveolar PCO2, CO2 production and heart rate were measured in eight normal subjects before and during infusions of noradrenaline 0.2, 1.0 and 5.0 micrograms min-1 and isoprenaline 0.04, 0.2 and 1.0 microgram min-1. 2 These measurements were repeated after propranolol 3.5 mg, atenolol 8 mg or meto...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb04961.x
更新日期:1982-11-01 00:00:00
abstract::1 To compare the haemodynamic effects of secondary characteristics of beta-adrenoceptor blockers with an angiotensin converting enzyme inhibitor forty patients with previously untreated mild to moderate hypertension were prescribed either atenolol 50-100 mg day-1, labetalol 200-800 mg day-1, pindolol 10-30 mg day-1 or...
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.1365-2125.1987.tb03157.x
更新日期:1987-08-01 00:00:00
abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:* Exposure to bosentan was lower in paediatric pulmonary arterial hypertension (PAH) patients treated with the marketed adult formulation at a dose of about 2 mg kg(-1) when compared with adult PAH patients. * In healthy adult subjects, bosentan pharmacokinetics are less than do...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1111/j.1365-2125.2009.03532.x
更新日期:2009-12-01 00:00:00
abstract:AIMS:Therapeutic drug monitoring of infliximab can guide clinical decisions in patients with loss of response and in those who can benefit from a de-intensification. The aim of this study was to determine the impact of therapeutic drug monitoring combined with Bayesian forecasting methodology on clinical response in a ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14410
更新日期:2020-06-03 00:00:00
abstract::1. The potential interaction between selective beta 1-adrenoceptor blockers and sulphonylureas or biguanides was studied by comparing the beta 1-adrenoceptor antagonist betaxolol with placebo in 12 normal subjects taking glibenclamide or metformin in a single-blind crossover group study. 2. After a 4 day run-in period...
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.tb03838.x
更新日期:1990-11-01 00:00:00
abstract::The importance of number of tablets for patient compliance was investigated in 160 patients with mild-moderate essential hypertension treated with a beta-adrenoceptor blocker and a thiazide diuretic. Mean BP at entry 146 +/- 16/92 +/- 8 mm Hg. All patients were given pindolol 10 mg and clopamide 5 mg in one combinatio...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1984.tb02388.x
更新日期:1984-05-01 00:00:00
abstract:AIM:Omalizumab, a humanized IgG monoclonal antibody that binds to human immunoglobulin E (IgE), interrupts the allergic cascade in asthmatic patients. The aim was to compare simultaneously drug exposure and IgE biomarker responses in Japanese and White patient populations. METHODS:An instantaneous equilibrium drug-lig...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2125.2006.02803.x
更新日期:2007-05-01 00:00:00
abstract::1. The N-acetylation of dapsone (DDS) was studied in 182 unrelated healthy Japanese subjects. The frequency of slow acetylators determined using the plasma monoacetyldapsone (MADDS) to DDS ratio (MADDS/DDS, slow acetylators less than 0.30 and rapid acetylators greater than 0.35) at 3 h after an oral dose of DDS (100 m...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb03333.x
更新日期:1988-04-01 00:00:00
abstract:AIMS:In order to evaluate a hypothesized protective effect of the use of HMG Co-A reductase inhibitors (statins) on the development of Type 2 diabetes, we conducted a nested case-control study based on data from the UK-based General Practice Research Database (GPRD). METHODS:We identified a population of adults 30-79 ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2004.02142.x
更新日期:2004-09-01 00:00:00
abstract:AIMS:We investigated whether the deterioration in asthma control reported following cessation of theophylline was due to tolerance to theophylline. METHODS:Eighteen subjects with mild stable asthma were given oral theophylline 10 mg kg(-1) day(-1) or placebo for 2 weeks in a double-blind crossover study. FEV1 and PD20...
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.t01-1-00691.x
更新日期:1998-04-01 00:00:00
abstract:ADVERSE EVENT:Repeated and prolonged episodes of central apnoea and hypoxia after receiving intravenous morphine for analgesia and ketamine for sedation. DRUG IMPLICATED:Intravenous morphine sulfate. THE PATIENT:Previously healthy 12-year-old male with no history of sleep apnoea who presented with distal tibia and fi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13779
更新日期:2019-01-01 00:00:00
abstract::1. The relative bioavailability of cyclosporin was studied in 11 healthy volunteers after single oral capsule doses of cyclosporin on three separate occasions; fasting, with breakfast and with breakfast together with bile acid tablets (400 mg of cholic acid and 100 mg of dehydrocholic acid). 2. There was a significant...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb03677.x
更新日期:1990-05-01 00:00:00