Abstract:
:1. Azole antifungal agents such as ketoconazole act by inhibiting cytochrome P-450 mediated sterol synthesis in the fungal cell membrane and thus have the potential to interfere with mammalian steroidogenesis. Fluconazole is a novel orally-effective antifungal triazole which has been reported to have more specific effects on the cytochrome P-450 enzymes involved in fungal sterol synthesis. 2. Due to the potential value of systemic antifungal agents in the treatment of infections commonly occurring in women, we assessed the effect of oral fluconazole on the metabolic profile of 18 healthy premenopausal women, 10 of whom were taking combined oral contraceptives (OC). Each woman acted as her own control, being studied both before and 21-28 days after fluconazole therapy (50 mg daily), in the luteal phase of consecutive menstrual cycles. 3. The endocrinological profile included measurement of serum oestradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) concentrations, short tetracosactrin adrenal stimulation test and thyroid function tests. Carbohydrate metabolism was investigated by means of an oral glucose tolerance test with measurement of plasma glucose, insulin and C-peptide concentrations. Serum lipids, lipoproteins and apolipoproteins were analysed on samples taken after an overnight fast. 4. Minor biochemical changes associated with fluconazole treatment included increases in serum thyroxine and testosterone concentrations (but not in women taking OC as well as fluconazole) and in insulin and apolipoprotein B levels (but only in women taking OC as well as fluconazole). In general, these changes were small and of no clinical significance with the values remaining within the laboratory normal range. There were no adverse side-effects.(ABSTRACT TRUNCATED AT 250 WORDS) :The metabolic effects of the anti-fungal drug fluconazole were investigated in 18 women, 10 of whom were taking oral contraceptives, to examine whether this steroid antagonist has any effects primarily on hormone systems. The women, aged 29-40, took 50 mg fluconazole orally from Day 1 of their menstrual cycle for 21-28 days. Subjects kept a symptom diary, were tested weekly for hematological and liver function, and were checked for compliance by analyzing blood for drug by GLC. 5 women reported side effects: somnolence, dizziness, fatigue, increased appetite, headache (1) and nausea (1). No effects on liver function or menses were noted. The only significant findings were increases in serum thyroxine and testosterone in fluconazole-only subjects, and increases in insulin and apo-lipoprotein B in fluconazole-oral contraceptive subjects. Pills containing levonorgestrel were used by 9 women, desogestrel by 1. No significant differences were seen in estradiol, progesterone, sex-hormone-binding globulin, thyroid function, cortisol, glucose, C-peptide, cholesterol, triglycerides, lipoproteins. Thus it is unlikely that the short-term use of fluconazole for treatment of superficial mycoses, such as vulvovaginal candidiasis, will adversely affect steroid metabolism in women.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Devenport MH,Crook D,Wynn V,Lees LJdoi
10.1111/j.1365-2125.1989.tb03449.xsubject
Has Abstractpub_date
1989-06-01 00:00:00pages
851-9issue
6eissn
0306-5251issn
1365-2125journal_volume
27pub_type
临床试验,杂志文章abstract::1. Kenyan children with uncomplicated malaria given oral halofantrine (HF; non-micronised suspension; 8 mg base kg-1 body weight 6 hourly for three doses) showed wide variation in the disposition of HF and desbutylhalofantrine (HFm). 2. Eight Kenyan children with severe (prostrate) falciparum malaria who were receivin...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1995.tb04450.x
更新日期:1995-03-01 00:00:00
abstract::1 Fourteen hypertensive patients were studied by intra-arterial BP monitoring to quantify the effects of standardized physiological stresses: Valsalva manoeuvre, isometric, treadmill and bicycle exercise, and 60 degree tilting before and after labetalol treatment. 2 The dose of labetalol ranged from 100--600 mg three ...
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:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Desmopressin is a known haemostatic agent and is also being used, albeit at lower doses, during the diagnostic work-up of Cushing's syndrome, a condition characterized by excess cortisol concentrations and frequent thromboembolic events. No study has yet evaluated whether admini...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2010.03812.x
更新日期:2011-01-01 00:00:00
abstract::1 Apparent Vmax and Km for phenytoin were estimated in 40 children (aged 8--33 months) and 21 adults (aged 18--66 years). 2 The derived values of Vmax and Km were used to predict the plasma and salivary concentrations of phenytoin following a change in dose. There was a highly significant correlation between observed ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1981.tb01285.x
更新日期:1981-11-01 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. Dose response relationships for salbutamol and a new bronchodilator drug NAB 365 have been obtained in patients with reversible airways obstruction. These show that the latter is about one hundred times more potent than the former. 2. NAB 365 has a very long half-life. The implications of this are discussed. ...
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.1365-2125.1977.tb00669.x
更新日期:1977-02-01 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 heart rate responses to increasing doses of isoprenaline (n = 6) (during infusion with atropine 0.5 mg/min i.v.) and noradrenaline (n = 5), (during infusion with phentolamine 160 mg/h i.v.) were recorded before and after the intravenous administration of propranolol (15 mg) or metoprolol (15 mg). 2 In the doses ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb01911.x
更新日期:1982-01-01 00:00:00
abstract:AIM:To evaluate safety, tolerability and pharmacokinetics of oral PF-05190457, an oral ghrelin receptor inverse agonist, in healthy adults. METHODS:Single (SAD) and multiple ascending dose (MAD) studies were randomised, placebo-controlled, double-blind studies. Thirty-five healthy men (age 38.2 ± 10.4 years; body mass...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.13127
更新日期:2017-02-01 00:00:00
abstract:AIMS:Navoximod (GDC-0919, NLG-919) is a small molecule inhibitor of indoleamine-2,3-dioxygenase 1 (IDO1), developed to treat the acquired immune tolerance associated with cancer. The primary objectives of this study were to assess navoximod's absolute bioavailability (aBA), determine the mass balance and routes of elim...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13961
更新日期:2019-08-01 00:00:00
abstract:AIMS:Breakthrough bleeding or even unwanted pregnancies have been reported in women during concomitant therapy with oral contraceptives and St John's wort extract. The aim of the present study was to investigate the effects of St John's wort extract on oral contraceptive therapy with respect to ovarian activity, breakt...
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.1365-2125.2003.02005.x
更新日期:2003-12-01 00:00:00
abstract:AIMS:This study aimed to develop a population pharmacokinetic model for quantitative evaluation of the influence of genetic variants in metabolic enzymes and transporters on lamotrigine pharmacokinetics while taking into account the influence of various clinical, biochemical and demographic factors. METHODS:We include...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/bcp.12984
更新日期:2016-08-01 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:AIM:We aimed to establish a method to assess systemic and pre-systemic cytochrome P450 (CYP) 3A activity using ineffective microgram doses of midazolam. METHODS:In an open, one sequence, crossover study, 16 healthy participants received intravenous and oral midazolam at microgram (0.001 mg intravenous and 0.003 mg ora...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12502
更新日期:2015-02-01 00:00:00
abstract:AIMS:Tolcapone is a novel catechol-O-methyltransferase (COMT) inhibitor used as an adjunct to levodopa/carbidopa or levodopa/benserazide therapy to improve treatment of Parkinson's disease. The aim of the current study was to investigate the potential effect of tolcapone on the pharmacokinetics of carbidopa. METHODS:T...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2125.1999.00027.x
更新日期:1999-09-01 00:00:00
abstract:AIMS:To investigate uptake of fluconazole into the interstitial fluid of human subcutaneous tissue using the microdialysis and suction blister techniques. METHODS:A sterile microdialysis probe (CMA/60) was inserted subcutaneously into the upper arm of five healthy volunteers following an overnight fast. Blisters were ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2003.01930.x
更新日期:2003-11-01 00:00:00
abstract::The influence of cimetidine pretreatment on the pharmacokinetics of 5-fluorouracil (5FU) has been studied in 15 ambulant patients with carcinoma. Neither pretreatment with a single dose of cimetidine (400 mg) nor with daily treatment at 1000 mg for 1 week altered 5FU pharmacokinetics. Pretreatment with cimetidine for ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02484.x
更新日期:1984-09-01 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:AIMS:Nicotine nasal spray and transdermal nicotine are effective aids to smoking cessation, and are being evaluated for treatment of other medical diseases. Wide variation in levels of nicotine and its metabolite, cotinine, have been observed with such therapies. This study aimed primarily to assess sources of individu...
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.1365-2125.1997.00566.x
更新日期:1997-03-01 00:00:00
abstract::Voriconazole is an antifungal metabolised by CYP2C19 enzyme, which can be inhibited by proton-pump inhibitors (PPIs). A prospective observational study was carried out to determine the influence of PPIs on voriconazole pharmacokinetic. The 78 patients included were divided into 4 groups: omeprazole (n = 32), pantopraz...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14267
更新日期:2020-08-01 00:00:00
abstract:AIMS:To determine whether topical ocular chloramphenicol increases the risk of aplastic anaemia and to estimate the magnitude of this risk, if any. METHODS:Population-based prospective case-control surveillance of aplastic anaemia in a community of 4.2 million inhabitants from 1980 to 1995 (67.2 million person-years) ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.1998.00773.x
更新日期:1998-08-01 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:AIMS:To measure the prevalence of beta-blocker eye drop prescribing and respiratory effect of ocular beta-blocker administration in people with asthma. METHODS:We measured the prevalence of ocular beta-blocker prescribing in people with asthma and ocular hypertension, and performed a nested case-control study (NCCS) m...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1111/bcp.13006
更新日期:2016-09-01 00:00:00
abstract::The mydriatic response to eyedrops of the anticholinergic drug tropicamide at very low concentration (0.01%) was studied in subjects with Alzheimer's disease (AD, n = 10) and multi-infarct dementia (MID, n = 10). There was no significant difference in pupillary response between the two groups. The test is unlikely to ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1996.tb00194.x
更新日期:1996-03-01 00:00:00
abstract::1. Potential therapies for ischaemic stroke include agents to reduce oedema, to improve cerebral perfusion, to reduce excitotoxic damage, to minimise free-radical induced injury and to reduce complications such as deep venous thrombosis. 2. Of the anti-oedema drugs, steroids are ineffective and possibly dangerous; int...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.1992.tb05655.x
更新日期:1992-12-01 00:00:00
abstract::Studies were done to examine the influence of the menstrual cycle on the elimination kinetics of paracetamol. Salivary concentrations of paracetamol were determined after oral administration of 1 g of paracetamol on day 3, 10, 14, 20 and 25 of the menstrual cycle in normal healthy women volunteers with regular menstru...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1987.tb03056.x
更新日期:1987-03-01 00:00:00
abstract::A free lignocaine index was developed on the basis of measurements of plasma lignocaine and its principle binding protein, alpha 1-acid glycoprotein (AAG) in 80 samples from 16 patients admitted to the coronary care unit and given prophylactic lignocaine therapy. The free drug fraction, fu, of lignocaine was determine...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb05132.x
更新日期:1985-12-01 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::Nine young and 12 elderly healthy volunteers received nisoldipine 10 mg once a day for 7 days. Plasma nisoldipine concentrations were measured on Day 1 and on Day 7. Higher plasma drug concentrations were observed in the elderly group than in the young group with the values for AUC being approximately doubled in the e...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1991.tb05547.x
更新日期:1991-03-01 00:00:00
abstract:AIMS:To compare single- and multiple-dose duloxetine pharmacokinetics between healthy Japanese and Caucasians. METHODS:Twenty-four subjects of each race were given single oral doses of duloxetine (20, 40 and 60 mg) in a randomized, double-blind study. Another 20 subjects of each race received 20, 40 mg or placebo (2 :...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2006.02770.x
更新日期:2007-03-01 00:00:00