Abstract:
PURPOSE:To investigate if the ordinary use of a vaginal suppository containing miconazole results in systemic absorption that is sufficient to affect the activities of CYP1A2 and CYP3A4, which are major drug- and steroid-metabolising enzymes. METHODS:In 20 healthy non-pregnant women aged 18-45 years, the serum concentration of miconazole was determined following the use of a vaginal suppository containing 1,200 mg miconazole. Enzyme activities of CYP1A2 and CYP3A4 were determined as metabolic ratios of caffeine (CMR = (AFMU + 1MU + 1MX)/17DMU) and quinidine (QMR = 3-hydroxy-quinidine/quinidine) respectively before and 34 h after insertion of the suppository. Miconazole was analysed by LC-MS/MS, while caffeine and metabolites were analysed by HPLC-UV and quinidine and hydroxy-quinidine were analysed by HPLC fluorescence. RESULTS:All 20 women had measurable concentrations of miconazole in serum (mean ± SD: 12.9 ± 5.6 μg/L; range: 3.5-24.6 μg/L). Although not statistically significant, an association between the serum concentrations of miconazole and the inhibition of CYP1A2 activity was indicated. No relation was observed between the CYP3A4 activity and the miconazole serum concentration. CONCLUSIONS:Miconazole is absorbed via the vaginal mucosa to the systemic circulation in measurable concentrations. Our data indicate a concentration-dependent inhibition of CYP1A2, but the effect is negligible compared with the variation in the activity of CYP1A2 and is regarded to be of no clinical significance to the women. However, further studies on the ability of miconazole to be transferred across the placenta or to interfere with the placental function are warranted to secure safe use during pregnancy.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Kjærstad MB,Nielsen F,Nøhr-Jensen L,Zwisler S,Brøsen K,Andersen HRdoi
10.1007/s00228-010-0906-2subject
Has Abstractpub_date
2010-12-01 00:00:00pages
1189-97issue
12eissn
0031-6970issn
1432-1041journal_volume
66pub_type
杂志文章abstract::We have studied the transfer of the analgesic ketorolac tromethamine into breast milk in ten women aged between 22 and 35 years. Ketorolac administration was started between 2 and 6 days after delivery. The breast milk was not fed to the infant because of maternal antibiotic use (6 patients) or because of jaundice of ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558080
更新日期:1989-01-01 00:00:00
abstract::The confidence interval approach to bioavailability assessment depends first on selection of the confidence level, usually 95%, and then determination of the confidence limits for the expected bioavailability ratio AUC(Test)/AUC(Reference). In practice, however, it is sometimes of greater interest to know the probabil...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00635713
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abstract:PURPOSE:The purpose of this study is to investigate the association between migration status and education level and the use of recommended drugs after first acute myocardial infarction (MI). METHODS:A nationwide cohort study performed in Sweden from January 1, 2006 to August 1, 2008. The cohort consisted of 49,037 in...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1821-3
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00609592
更新日期:1981-01-01 00:00:00
abstract::To assess the partial agonist activity of cicloprolol in man, four studies were carried out in normal male volunteers. I and II. Open dose escalating studies of the effects of oral doses of the drug on exercise tachycardia and sleeping heart rate. III and IV. Double-blind randomized studies of the effects of placebo, ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00615219
更新日期:1988-01-01 00:00:00
abstract::In a cross-over study of six healthy male volunteers, 500 mg theophylline was administered either as plain tablets or in a sustained release preparation. On each occasion 2 g of non-enteric coated sulphasalazine was administered simultaneously as the time of appearance of sulphapyridine, the product of hydrolysis, in ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00265979
更新日期:1990-01-01 00:00:00
abstract:OBJECTIVES:To identify the frequency of CYP2C9*1, *2 and *3 alleles and the genotype of CYP2C9 gene in the Tamilian population. METHODS:The study was conducted on 135 unrelated healthy human volunteers. DNA was extracted from the peripheral leukocytes samples and was analyzed using the polymerase chain reaction (PCR)-...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-003-0666-3
更新日期:2003-11-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
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更新日期:2009-05-01 00:00:00
abstract::The metabolism of hydralazine in a group of slow acetylator patients with the drug-induced lupus syndrome was compared with the metabolism in asymptomatic control subjects. There were no toxicologically significant difference in metabolite excretion between the groups which reached statistical significance, although t...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00556891
更新日期:1984-01-01 00:00:00
abstract::Sixty patients were treated for 1 year for essential uncomplicated hypertension, 30 with beta-blockers alone (BB) and 30 with BB and chlorthalidone (CTD). BB did not affect serum K+ or Mg++. In the BB-group there was a statistically significant trend towards retention of Mg++ in a loading test, but the effect was clin...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00543964
更新日期:1987-01-01 00:00:00
abstract::The hypothesis has been tested that an unusual maternal acetylator phenotype can predispose to congenital malformations in the fetus. The acetylator phenotype of normal caucasian control women and of mothers of malformed children was established by measuring urinary sulphadimidine and its acetylated metabolite. A furt...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00609187
更新日期:1989-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2017-03-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00613426
更新日期:1975-10-10 00:00:00
abstract:AIMS:Our objectives were to assess the detection and incidence of drug-induced agranulocytosis in two university hospitals using hematology laboratory data. METHODS:A prospective study was undertaken at Toulouse University Hospital (France) and Navarra University Hospital (Spain) for 1 year (from 1 May 2004 to 30 Apri...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-006-0242-8
更新日期:2007-03-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00316093
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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abstract::Ten normal adult tobacco smokers and 10 nonsmoking volunteers 20-31 years of age were the subjects of this study. The tobacco smokers all had a history of daily tobacco smoking. They were asked to stop smoking for 12 hours prior to testing. The Hoffmann (H) reflex and its recovery cycle were measured on different days...
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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更新日期:1979-11-01 00:00:00
abstract::The diabetogenic effect of deflazacort (DF), an oxazolinic synthetic corticosteroid, was studied in 12 healthy adult subjects with a positive family history of diabetes mellitus. Three oral glucose tests (oGTT) were performed at 9.00 a.m., after a 12 h fast, following randomized administration of Placebo (PL), or Defl...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00542555
更新日期:1982-01-01 00:00:00
abstract::In 12 patients undergoing coloscopy, 0.5 mg digoxin in aqueous alcoholic solution was injected into the transverse colon. The late maximum of the blood level curve at about 2 hours after the administration suggested delayed absorption of the glycoside. However, the 24 hour urinary excretion of 17 +/- 3.4% in 8 patient...
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pub_type: 杂志文章
doi:10.1007/BF00614003
更新日期:1975-12-19 00:00:00
abstract::The effect of the GABAergic drug sodium valproate (SV) on the exercise-induced release of growth hormone (GH) was investigated in 10 healthy males. The exercise test consisted of using a stationary bicycle ergometer at 450 kg/min for 20 min. SV 600 mg blunted the increase in GH induced by the exercise, suggesting GABA...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00544075
更新日期:1985-01-01 00:00:00
abstract::The sulphation of (+) and (-) terbutaline was investigated in specimens of human intestinal mucosa isolated from the duodenum, ileum, ascending colon and sigmoid colon and in specimens of liver and lung. The lung specimens came from 8 current smokers and 11 ex-smokers, the latter having stopped at least 3 months befor...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315522
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:Neuroblastoma is the most common extracranial solid tumour in childhood. It accounts for 15% of all paediatric oncology deaths. In the last few decades, improvement in treatment outcome for high-risk patients has not occurred, with an overall survival rate <30-40%. Many reasons may account for such a low surviv...
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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abstract::In this paper an alternative approach to nonlinear pharmacokinetics modelling has been developed from first principles. This "Unsteady Model" is able to describe the situation whereby one or more independent drugs and their metabolites compete for free attachment sites in liver, tissue, red blood cells etc. The Unstea...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00615410
更新日期:1981-01-01 00:00:00
abstract:PURPOSE:Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction. This study was aimed to evaluate ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-016-2062-9
更新日期:2016-08-01 00:00:00
abstract::To evaluate the possible effect of quinidine on digoxin bioavailability, the steady state digoxin kinetics was examined with and without concomitant quinidine therapy, in 7 cardiac patients after simultaneous administration of oral digoxin and intravenous [3H]-digoxin. In the presence of quinidine, the absorption rate...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:1983-01-01 00:00:00