Abstract：
AIMS:Voriconazole is a novel triazole with broad-spectrum antifungal activity. It is likely that some patients receiving voriconazole may also require treatment with the anticoagulant warfarin. Cytochrome P450 isoenzymes are important in the metabolism of both these drugs. This study investigated the effect of voriconazole on the pharmacodynamics of warfarin by measuring prothrombin time, and also evaluated the safety and tolerability of the coadministered drugs. METHODS:This was a double-blind, placebo-controlled, two-way crossover study in which healthy male subjects received either 300 mg voriconazole or placebo twice daily on days 1-12, plus a single oral dose of 30 mg warfarin on day 7 of each study period. Volunteers were randomized to one of the following treatment sequences: voriconazole + warfarin followed by placebo + warfarin or placebo + warfarin followed by voriconazole + warfarin. There was a washout of at least of 7 days between treatment periods. RESULTS:The mean Cmax, AUCtau and tmax for voriconazole were 3736 ng ml-1, 25 733 ng.h ml-1, and 1.66 h, respectively. Both the mean maximum change from baseline prothrombin time and the mean area under the effect curve (AUEC) for prothrombin time during coadministration with voriconazole (17 s and 3211 s.h, respectively) were statistically significantly greater than the mean values observed during the placebo period (8 s and 2282 s.h ). Prothrombin times were still increased by a mean value of 5.4 s 144 h post warfarin dose following coadministration with voriconazole compared with a mean value of 0.6 s in the placebo treatment period. CONCLUSIONS:Coadministration of voriconazole and warfarin potentiates warfarin-induced prothrombin time prolongation. Regular monitoring of prothrombin time is recommended if these drugs are coadministered, with appropriate adjustment of the dose of warfarin.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Purkins L,Wood N,Kleinermans D,Nichols Ddoi
10.1046/j.1365-2125.2003.01995.xkeywords:
subject
Has Abstractpub_date
2003-12-01 00:00:00pages
24-9eissn
0306-5251issn
1365-2125pii
1995journal_volume
56 Suppl 1pub_type
临床试验,杂志文章,随机对照试验abstract：AIMS:To investigate the effect of multiple dosing with montelukast, a selective leukotriene-receptor antagonist, on the pharmacokinetics of rosiglitazone, a CYP2C8 substrate, in humans. METHODS:A two-period, randomized crossover study was conducted in 10 healthy subjects. After administration of oral doses of placebo ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1365-2125.2006.02764.x
更新日期：2007-03-01 00:00:00
abstract：:Twelve patients with acute uncomplicated falciparum malaria were admitted to the Hospital for Tropical Diseases for 42 days. The patients were treated with halofantrine 500 mg 6 hourly for three doses and halofantrine and its desbutyl metabolite were analysed in plasma by h.p.l.c. Cmax values of halofantrine and desbu...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1991.tb05567.x
更新日期：1991-04-01 00:00:00
abstract：:Since many factors may alter lung epithelial permeability (LEP) to water soluble molecules, the effect of histamine on the absorption and clearance of inhaled sodium cromoglycate was examined in seven mildly asthmatic patients with hyperresponsive airways and eight normal subjects. The subjects underwent histamine cha...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1992.tb04048.x
更新日期：1992-03-01 00:00:00
abstract：:The effect of metronidazole, at a dose of 1.2 g daily, on theophylline disposition was studied in 10 healthy adult volunteers. Neither theophylline half-life, volume of distribution nor total body clearance was altered by the anti-microbial. It is concluded that metronidazole does not impair theophylline metabolism de...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1987.tb03146.x
更新日期：1987-07-01 00:00:00
abstract：:1. The pharmacokinetics of physostigmine were investigated in a three-way cross-over design in six healthy, male volunteers comparing a physostigmine transdermal system (PTS), an oral solution and an i.v. infusion. 2. A single application of the patch over 24 h produced detectable plasma drug concentrations after a me...
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.1365-2125.1995.tb04410.x
更新日期：1995-01-01 00:00:00
abstract：BACKGROUND:Benzodiazepines and "Z drugs" are often prescribed in residents of nursing homes (NH) despite their well-known deleterious effects. We aimed to investigate if a general intervention on quality of care led to discontinuation of benzodiazepine, and to examine which NH-related factors were associated in change ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.12847
更新日期：2016-04-01 00:00:00
abstract：AIM:To assess the relative contribution of intestinal and hepatic CYP3A inhibition to the interaction between the prototypic CYP3A substrate midazolam and clarithromycin in the elderly. METHODS:On day 1, 16 volunteers (eight male, eight female) aged 65-75 years weighing 59-112 kg received simultaneous doses of midazol...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.2007.02970.x
更新日期：2008-01-01 00:00:00
abstract：WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Rotigotine transdermal patch is a new non-ergolinic dopamine agonist developed for the treatment of Parkinson's disease and restless legs syndrome. Peripheral dopaminergic side-effects of dopamine agonists such as nausea and vomiting can be prevented by the antiemetic agent domp...
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.1365-2125.2008.03334.x
更新日期：2009-02-01 00:00:00
abstract：:1 Six previously untreated emergency admissions to hospital with severe hypertension were given oral treatment with labetalol. 2 Pre-treatment diastolic BP exceeded 130 mmHg, and clinical evidence of either accelerated hypertension or encephalopathy was present. 3 Hypotensive response after treatment followed two patt...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1979-01-01 00:00:00
abstract：:Early clinical features of lead toxicity are non-specific and an occupational history is particularly valuable. Lead in the body comprises 2% in the blood (t1/2 35 days) and 95% in bone and dentine (t1/2 20-30 years). Blood lead may remain elevated for years after cessation from long exposure, due to redistribution fr...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2002.01580.x
更新日期：2002-05-01 00:00:00
abstract：AIMS:Helicobacter pylori (H. pylori) eradication rate varies according to the treatment regimen used and other factors, e.g. antimicrobial resistance and patient compliance. The aim of the present study was to evaluate the influence of patient counselling and follow-up on H. pylori eradication rates and to document the...
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.0306-5251.2001.01531.x
更新日期：2002-02-01 00:00:00
abstract：:The steady-state pharmacokinetic interaction between nefazodone and cimetidine was evaluated in a three-period crossover study consisting of three treatments of 1 week duration with a 1 week washout between treatments. The 18 healthy, male study subjects received: nefazodone hydrochloride 200 mg twice daily (every 12 ...
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.1365-2125.1995.tb05771.x
更新日期：1995-08-01 00:00:00
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 'p...
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.1365-2125.1996.tb00114.x
更新日期：1996-11-01 00:00:00
abstract：AIMS:Recently, an apparent protective effect of statins against upper gastrointestinal bleeding (UGB) was postulated in a post hoc analysis of a randomized trial. We aimed to evaluate the effect of statin use on acute nonvariceal UGB alone or in combinations with low-dose aspirin and other antithrombotic drugs. METHOD...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2009.03362.x
更新日期：2009-04-01 00:00:00
abstract：:Despite the revolution in recent decades regarding monoamine involvement in the management of major depressive disorder (MDD), the biological mechanisms underlying this psychiatric disorder are still poorly understood. Currently available treatments require long time courses to establish antidepressant response and a ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.12845
更新日期：2016-11-01 00:00:00
abstract：:1 Ten consecutive patients with hypertriglyceridaemia who adhered to a low carbohydrate diet without complete control of serum triglycerides were started on chenodeoxycholic acid 750 mg daily and followed monthly for 6 months. Nine of these patients were then followed for a further month on placebo capsules and therea...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1978.tb01632.x
更新日期：1978-03-01 00:00:00
abstract：AIMS:There is a trend for more flexibility in timing of evidence generation in relation to marketing authorization, including the option to complete phase III trials after authorization or not at all. This paper investigated the relation between phase II and III clinical trial efficacy in oncology. METHODS:All oncolog...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14237
更新日期：2020-07-01 00:00:00
abstract：AIMS:Changes in both digoxin and aciclovir renal clearance following coadministration with some other renally eliminated drugs have been reported. The potential interaction of valaciclovir, with its antiherpetic metabolite aciclovir, and digoxin was investigated. METHODS:Twelve healthy volunteers (seven males, five fe...
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.1365-2125.1998.00649.x
更新日期：1998-01-01 00:00:00
abstract：:1. Six healthy male human volunteers of mean age 30.8 years (range 23-37) were given single oral doses of xamoterol (20, 50, 100 or 250 mg) and placebo with a 1 week interval between each dose. Xamoterol produced a significant decrease in systolic time intervals (QS2I, LVETI and PEPI) and a significant increase in sys...
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.tb03663.x
更新日期：1990-04-01 00:00:00
abstract：AIMS:Topical growth factors accelerate wound healing in patients with diabetic foot ulcers (DFU). Due to the absence of head-to-head comparisons, we carried out Bayesian network meta-analysis to compare the efficacy and safety of growth factors. METHODS:Using an appropriate search strategy, randomized controlled trial...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,meta分析
doi：10.1111/bcp.13470
更新日期：2018-03-01 00:00:00
abstract：AIMS:Aldosterone has been found to influence cancer cell growth, cell cycle regulation and cell migration, including in prostate cancer cells. Spironolactone is an aldosterone antagonist used for managing chronic heart failure (HF) with known antiandrogenic effects. We examined the effect of spironolactone exposure amo...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14568
更新日期：2020-09-28 00:00:00
abstract：:The effects of omeprazole on cytochrome P-450 mediated 7-ethoxycoumarin deethylation were studied in human liver microsomes. Omeprazole inhibited both the high and low affinity components of deethylation, with an estimated Ki of 0.03 mM for the high affinity component. The results are further evidence that the previou...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1986.tb05199.x
更新日期：1986-03-01 00:00:00
abstract：:Renal clearance of lithium has been used as a marker of proximal tubular function in man. Recently, lithium pre-treatment has been shown to interfere with the natriuretic actions of some natriuretic agents in man. We have therefore investigated the effects of oral lithium carbonate (500 mg) on the natriuretic response...
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.tb05598.x
更新日期：1991-06-01 00:00:00
abstract：AIMS:Major bleeding complications with low-molecular-weight heparin (LMWH) treatment have been reported both in clinical studies and during postmarketing surveillance. Monitoring of antifactor Xa (anti-Xa) activities is therefore recommended in special populations often predisposed to renal impairment. The PROPHRE.75 s...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2007.02920.x
更新日期：2007-10-01 00:00:00
abstract：:1. The dose-peak effect relationship of lisinopril was evaluated in a double-blind, parallel study in 83 patients with mild to moderate essential hypertension (supine diastolic blood pressure = 95-115 mm Hg). 2. After a 4 week placebo washout, patients were randomly assigned to one of four treatments: lisinopril 2.5, ...
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.tb03342.x
更新日期：1988-05-01 00:00:00
abstract：:The single oral dose pharmacokinetics of carbamazepine-10, 11-epoxide (CBZ-E) were investigated in six normal volunteers during a control session and during concurrent treatment with valpromide (VPM) (300 mg twice daily for 8 days). VPM caused a prolongation of the CBZ-E half-life from 6.4 +/- 1.4 to 20.5 +/- 6.3 h an...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1988.tb03354.x
更新日期：1988-05-01 00:00:00
abstract：:Theophylline clearance was studied in normal healthy volunteers before and after chronic oral dosing. Oral theophylline clearance showed a significant decrease (P less than 0.001) from 59.3 +/- 6.48 ml/min (mean +/- s.e. mean, n = 10) to 48.0 +/- 6.4 ml/min. Steady-state intravenous clearance decreased by 26 +/- 2% fr...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1984.tb02385.x
更新日期：1984-05-01 00:00:00
abstract：:Ouabain inhibits endothelium-dependent vascular relaxation in vitro, but has not been studied in this regard in vivo. We have therefore measured blood flow responses to carbachol, bradykinin and sodium nitroprusside (endothelium-dependent and endothelium-independent vasodilators) infused into the brachial artery with ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-12-01 00:00:00
abstract：AIMS:The main goal of the study was to describe the pharmacokinetics of maternal zidovudine (ZDV) administration during pregnancy and labour and to evaluate their impact on fetal concentrations and exposures. METHODS:A total of 195 HIV-infected pregnant and non-pregnant women aged 16-59 years were included and 273 mat...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.12459
更新日期：2014-12-01 00:00:00
abstract：:The pharmacokinetics of piroximone (PI) were determined in patients with renal failure (inulin clearance less than 50 ml min-1 per 1.73 m2) using two protocols: (a) 10 patients received a single i.v. infusion of 0.5 mg kg-1 PI and the data were compared with those from seven healthy subjects receiving the same regimen...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1995.tb04429.x
更新日期：1995-02-01 00:00:00
