Abstract:
OBJECTIVE:To study the influence of CYP3A4 inhibition by ketoconazole on the disposition of venlafaxine in individuals with different CYP2D6 pheno- and genotypes. METHODS:In an open two-phase study, 21 healthy volunteers with known CYP2D6 pheno- and genotype [14 extensive metabolisers (EMs), 7 poor metabolisers (PMs)] were given a single oral dose of venlafaxine (50 mg to EMs and 25 mg to PMs). Plasma and urine levels of venlafaxine and its three metabolites were measured and the pharmacokinetics of venlafaxine were determined. After a 2-week washout period, subjects were treated for 2 days with ketoconazole (100 mg twice daily) starting 1 day before the administration of venlafaxine; and the same parameters as for the administration of venlafaxine only were measured. RESULTS:Data were evaluated from 20 subjects (14 EMs and 6 PMs) who completed the study. The dose-corrected AUC of venlafaxine was on average 2.3 times higher ( P<0.01) and that of its active metabolite O-desmethylvenlafaxine 3.4 times lower ( P<0.0001) in PMs than EMs. There was a good correlation between the debrisoquine metabolic ratio and the ratio between the AUC of venlafaxine and that of O-desmethylvenlafaxine ( Rs=0.93, P<0.002). The majority of subjects showed higher plasma levels of venlafaxine and O-desmethylvenlafaxine upon co-administration of ketoconazole. AUC of venlafaxine significantly increased by 36% and that of O-desmethylvenlafaxine by 26% ( P<0.01). C(max) values increased by 32% and 18%, respectively. The elimination half-life of venlafaxine was unaltered. Three of the PMs displayed marked increases in AUC (81, 126 and 206%) and C(max) (60, 72, 119%) of venlafaxine while the other three showed small or no changes. CONCLUSIONS:Ketoconazole consistently affected the disposition of venlafaxine in EMs of debrisoquine while the response in PMs was erratic. The precise mechanisms underlying this interaction remain to be elucidated.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Lindh JD,Annas A,Meurling L,Dahl ML,AL-Shurbaji Adoi
10.1007/s00228-003-0627-xsubject
Has Abstractpub_date
2003-09-01 00:00:00pages
401-6issue
5-6eissn
0031-6970issn
1432-1041journal_volume
59pub_type
临床试验,杂志文章abstract:PURPOSE:Concomitant treatment with the glucose-lowering drug metformin and the platelet aggregation inhibitor dipyridamole often occurs in patients with type 2 diabetes mellitus who have suffered a cerebrovascular event. The gastrointestinal uptake of metformin is mediated by the human equilibrative nucleoside transpor...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-016-2039-8
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abstract::Postural and isometric handgrip tests were performed on nine patients with panic disorder and 13 patients with major depression before and after treatment with imipramine for a mean duration of 10 weeks. There were significant increases in resting supine heart rate (HR), systolic, diastolic and mean blood pressures (S...
journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,meta分析
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更新日期:2014-04-01 00:00:00
abstract:AIMS:The goal of this study was to analyze persistence and the treatment-free interval in patients being prescribed biological drugs in rheumatology practices in Germany. METHODS:Patients who received a first prescription of biological drugs between 2008 and 2016 in 21 rheumatologists in Germany were included in this ...
journal_title:European journal of clinical pharmacology
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doi:10.1007/s00228-019-02627-y
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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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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:1992-01-01 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
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:2010-03-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2002-01-01 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
doi:10.1007/s002280050127
更新日期:1996-01-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-005-0914-9
更新日期:2005-06-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
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更新日期:2008-01-01 00:00:00
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更新日期:2013-03-01 00:00:00
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journal_title:European journal of clinical pharmacology
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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:1998-09-01 00:00:00
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更新日期:2013-04-01 00:00:00
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更新日期:2013-10-01 00:00:00
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