Abstract:
:1. The pharmacokinetics of proguanil were evaluated in patients with acute P. falciparum malaria receiving concomitantly proguanil hydrochloride and atovaquone. The population consisted of 203 Blacks, 112 Orientals and 55 Malays; 274 males and 96 females. Of the 370 patients, 114 and 256 patients were classified as 'poor' and 'extensive' metabolizers of proguanil, respectively. Body weight and age ranged between 11-110 kg and 3-65 years, respectively. 2. A one compartment model with first-order absorption and elimination was fitted to proguanil plasma concentration-time profiles, using non-linear mixed effect modelling (NONMEM). 3. Oral clearance (CLo) showed a 0.785 power relationship with body weight and was 13% higher in Orientals than Blacks and Malays and 17% lower in 'poor' than 'extensive' metabolizers. According to the mean weight of each population, the final population estimates of CLo in Blacks, Orientals and Malays who are 'extensive' metabolizers were 54.0, 61.5 and 64.3 l h-1, respectively. Age, gender and dose had no significant effects on CLo. 4. Apparent volume of distribution (V/F) showed a 0.88 power relationship with body weight. The final population estimates were 562 and 1629 l in children (< or = 15 years) and patients aged > 15 years, respectively, who had a mean body weight of 22.6 and 54.8 kg, respectively. The effect of other covariates on V/F was not examined. 5. The final magnitudes of interpatient variability in CLo and V/F were relatively low at 22.5 and 17.0%, respectively. 6. Population pharmacokinetic parameter estimates in Black, Oriental and Malay patients with acute P. falciparum malaria are in good agreement with results of pharmacokinetic studies in healthy Caucasian volunteers. In view of the 30-50% residual variability in proguanil plasma concentrations, the slight effects of Orientals and 'poor' metabolizers on CLo are unlikely to be clinically significant. Hence, dose recommendation will be solely based on body weight.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Hussein Z,Eaves CJ,Hutchinson DB,Canfield CJdoi
10.1111/j.1365-2125.1996.tb00114.xsubject
Has Abstractpub_date
1996-11-01 00:00:00pages
589-97issue
5eissn
0306-5251issn
1365-2125journal_volume
42pub_type
临床试验,杂志文章,随机对照试验abstract::1 The absorption of effervescent aspirin was studied in normal volunteers of both sexes under varied conditions of activity in both fasting and non-fasting states. 2 Moderate activity resulted in no significant changes in absorption compared with that at rest. 3 In non-fasting subjects the absorption was reduced but t...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1974.tb00222.x
更新日期:1974-04-01 00:00:00
abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Nitrates may facilitate syncope through various pathways, but the precise mechanism of nitrate-induced syncope is still under debate. The purpose of the present study was to compare the underlying haemodynamic mechanisms in subjects without and with presyncopal symptoms during a...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2010.03794.x
更新日期:2011-01-01 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 investigate the driving forces behind increasing utilization of cardiovascular drugs. METHODS:Using register data, all Danish residents as of 1 January 1996 were followed until 2006. Cohort members were censored at death or emigration. Cardiovascular drug utilization on the individual level was traced, applyin...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2125.2008.03282.x
更新日期:2008-12-01 00:00:00
abstract:AIMS:To investigate presence or absence of clinically relevant drug interactions (pharmacokinetic and safety/tolerability) of OBE022 with standard-of-care medicines for preterm labour, enabling coadministration and further clinical development. METHODS:Part A: open-label, randomized, 3-period crossover assessing coadm...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.13925
更新日期:2019-07-01 00:00:00
abstract::1. The absorption and disposition of paracetamol was investigated in 10 healthy male Thai vegetarians and 10 similar non-vegetarians following an oral dose of 20 mg kg-1. 2. The absorption rate of paracetamol was significantly impaired in the vegetarians compared with the non-vegetarians as shown by a lower mean Cmax ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1993.tb04223.x
更新日期:1993-09-01 00:00:00
abstract::Caffeine (5 mg kg-1) was administered orally to two healthy, non-smoking subjects on three separate occasions--before, and during therapy with the xanthine oxidase inhibitor allopurinol at doses of either 300 or 600 mg daily. Plasma and urinary levels of methylxanthines, endogenous oxypurines and allopurinol and its m...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1986.tb05222.x
更新日期:1986-04-01 00:00:00
abstract::1. Endogenous dopamine, acting through specific receptors on blood vessels, renal tubules and adrenal cortical cells, may play a role in the development and maintenance of the hypertensive state. 2. In hypertensive patients, activation of the DA1-receptor with intravenous fenoldopam produces a rapid and sustained redu...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.1990.tb05470.x
更新日期:1990-01-01 00:00:00
abstract::1 Previous studies of propranolol disposition in renal failure have been conflicting. 2 Using simultaneous administration of [3H]-propranolol intravenously and unlabelled propranolol orally the principal determinants of drug distribution were calculated in normals, patients with severe renal impairment (creatinine cle...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1980.tb00511.x
更新日期:1980-12-01 00:00:00
abstract::The effect of urinary pH on flecainide excretion has been evaluated in six healthy subjects after a single oral dose of 300 mg flecainide administered as the acetate salt. The cumulative urinary excretion of unchanged flecainide under acidic conditions (134.0 +/- 16.1 mg; mean +/- s.e. mean) was significantly higher t...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02370.x
更新日期:1984-04-01 00:00:00
abstract::1. Alfuzosin is a post-synaptic alpha-adrenoceptor antagonist with antihypertensive and peripheral vasodilator properties. 2. We measured the effect of alfuzosin, 5 mg, on sympathetically-mediated venoconstriction by changes in the venous reflex response (VRR) in a randomised, double-blind, placebo-controlled, crossov...
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.tb05330.x
更新日期:1989-01-01 00:00:00
abstract:AIMS:To evaluate the role of reported daily dose, age and other risk factors, and to assess the value of quantifying serum transaminase activity and paracetamol (acetaminophen) concentration at initial assessment for identifying patients at risk of hepatotoxicity following repeated supratherapeutic paracetamol ingestio...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.13028
更新日期:2016-10-01 00:00:00
abstract:AIMS:To evaluate the effect of a 3-day regimen of ibuprofen 600 mg x 4 on acute postoperative swelling and pain and other inflammatory events after third molar surgery compared with a traditional regimen of paracetamol 1000 mg x 4. METHODS:A controlled, randomized, double-blind, cross-over study where 36 patients (26 ...
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.1365-2125.2003.01779.x
更新日期:2003-04-01 00:00:00
abstract:AIMS:Surgical site infections contribute to morbidity and mortality after surgery. The authors hypothesized that higher antibiotic tissue concentrations can be reached for a prolonged time span by continuous administration of prophylactic cefuroxime compared to bolus administration. METHODS:Twelve patients undergoing ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13865
更新日期:2019-04-01 00:00:00
abstract:AIMS:The study was designed to evaluate the relative bioavailability of diclofenac in plasma, subcutaneous adipose and skeletal muscle tissue after repeated topical administration using MIKA Diclofenac Spray Gel (4%), a novel formulation, and after oral dosing using VOLTAREN 50 mg enteric coated tablets. METHODS:Diclo...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2005.02484.x
更新日期:2005-11-01 00:00:00
abstract::The effect of salbutamol on bronchoconstriction induced by inhaled sodium metabisulphite has been studied in 12 atopic subjects. Salbutamol (200 micrograms, 3.5 x 10(-7) M) and matched placebo were administered by identical metered dose inhaler 15 min before a dose-response to sodium metabisulphite (1.25-100 mg ml-1) ...
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.1365-2125.1991.tb03967.x
更新日期:1991-11-01 00:00:00
abstract:AIMS:To analyse clinical outcomes with direct oral anticoagulants in patients with atrial fibrillation according to geographic region. METHODS:We systematically searched MEDLINE, CENTRAL, websites of regulatory agencies, clinical trials registers and conference proceedings for randomized controlled trials of direct or...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1111/bcp.13005
更新日期:2016-09-01 00:00:00
abstract::1. The pharmacokinetics and pharmacodynamics of intranasal (IN) and oral 1-deamino-8-D-arginine vasopressin (DDAVP) were compared in 10 Chinese adults with central diabetes insipidus previously controlled on IN DDAVP. This was followed by comparison of the acute pharmacodynamics of commonly used oral preparations (con...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.1996.39914.x
更新日期:1996-09-01 00:00:00
abstract:AIM:The aim of this study was to investigate the effect of rectal ozone on portal vein oxygenation and the pharmacokinetic changes of propranolol in patients with liver cirrhosis. METHODS:Fifteen patients with liver cirrhosis were included They were given a fixed oral dose of propranolol 80mg on the morning of day 1 a...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2010.03851.x
更新日期:2011-03-01 00:00:00
abstract::1. In a double-blind, placebo-controlled, cross-over study, acute pharmacokinetic, neurophysiological and psychotropic effects of suriclone, a new cyclopyrrolone derivative, were investigated and compared with alprazolam. 2. Fifteen normal young volunteers received randomized oral single doses of placebo, 0.1, 0.2 and...
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.1365-2125.1994.tb04254.x
更新日期:1994-02-01 00:00:00
abstract::1. Nine healthy volunteers received 10 mg nitrendipine or placebo orally in random order. 2. In the subsequent 5 h urinary sodium excretion was 20% higher after nitrendipine, without any significant difference between the volume of urine excreted after nitrendipine or placebo. Mean blood pressure fell by 5 mm Hg (P le...
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.tb03817.x
更新日期:1990-10-01 00:00:00
abstract::Pharmacological interactions in both directions between phenprocoumon and atenolol and metoprolol were investigated using a crossover trial. Co-administration of phenprocoumon did not significantly affect Cmax, tmax, t1/2,22, AUC for atenolol or metoprolol. Co-administration of metoprolol, but not atenolol, increased ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02439.x
更新日期:1984-01-01 00:00:00
abstract:AIMS:The inhaled allergen challenge model has been used previously to investigate the effects of novel anti-inflammatory drugs in inhaled corticosteroid (ICS)-naïve asthmatics. The aim of this study was to characterize high- and low-dose allergen challenges in asthmatic patients using ICS. METHODS:Twenty-eight asthmat...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12508
更新日期:2015-03-01 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:A systematic review of the literature published in English over 10 years was undertaken in order to describe the use of electronic healthcare data in the identification of potential adverse drug reactions (ADRs) in children. METHODS:MEDLINE and EMBASE were searched using MESH headings and text words. Titles, keyw...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12645
更新日期:2015-10-01 00:00:00
abstract:PURPOSE:Prescribed daily dose (PDD), the number of doses prescribed to be taken per day, is used to calculate medication adherence using pharmacy claims data. PDD can be substituted by (i) one dose per day (1DD), (ii) an estimate based on the 75th percentile of days taken by patients to refill a script (PDD75 ) or (iii...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14468
更新日期:2020-07-08 00:00:00
abstract:AIMS:To study the impact of risperidone (RISP) on clozapine (CLZ) biotransformation in vitro in microsomal fractions containing varying expression of CYP oxidases and in vivo in patients. METHODS:Human liver microsomes (n= 11) were assessed for expression of CYPs 1A2, 2D6 and 3A4, because these enzymes mediate RISP an...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2125.2009.03476.x
更新日期:2009-10-01 00:00:00
abstract::1 A double-blind entry to a trial of an active non-steroidal anti-inflammatory drug, flurbiprofen against placebo was undertaken until 100 patients with classical rheumatoid arthritis had been allocated to each treatment. 2 Each patient was given a long-term supply of drug and was asked to vary their own dosage within...
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.1365-2125.1978.tb01654.x
更新日期:1978-05-01 00:00:00
abstract:AIMS:To determine role of CYP2D6 activity in the pharmacokinetics of propafenone (PPF) enantiomers in native Chinese subjects. METHODS:Sixteen extensive metabolizers (EMs) and one poor metabolizer (PM), whose phenotype had been previously assessed with dextromethorphan metabolic phenotyping, were enrolled. Blood sampl...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2125.1999.00932.x
更新日期:1999-05-01 00:00:00
abstract::Propranolol induced changes in blood plasma chemistry were followed in thirty hypertensive patients (WHO I-II) who were seen each week during 14-15 weeks. The initial 4 weeks were a drug free period and the next 2 weeks were a drug adjustment period. After that the patients were on an unchanged propranolol dose for 8 ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02341.x
更新日期:1984-03-01 00:00:00