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 transporter 4 (ENT4), which is inhibited by dipyridamole in preclinical studies. We hypothesized that dipyridamole lowers the plasma exposure to metformin. METHODS:Eighteen healthy volunteers (mean age 23 years; 9 male) were randomized in an open-label crossover study. Subjects were allocated to treatment with metformin 500 mg twice daily in combination with dipyridamole slow-release 200 mg twice daily or to metformin alone for 4 days. After a washout period of 10 days, the volunteers were crossed over to the alternative treatment arm. Blood samples were collected during a 10-h period after intake of the last metformin dose. The primary endpoint was the area under the plasma concentration-time curve (AUC0-12h) and the maximum plasma metformin concentration (C max). RESULTS:In healthy subjects, dipyridamole did not significantly affect Cmax nor AUC0-12h of metformin under steady-state conditions. CONCLUSIONS:Previous in vitro studies report that dipyridamole inhibits the ENT4 transporter that mediates gastrointestinal uptake of metformin. In contrast, co-administration of dipyridamole at therapeutic dosages to healthy volunteers does not have a clinically relevant effect on metformin plasma steady-state exposure. This observation is reassuring for patients who are treated with this combination of drugs.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
El Messaoudi S,Russel FG,Colbers A,Bandell CC,van den Broek PH,Burger DM,Rongen GA,Riksen NPdoi
10.1007/s00228-016-2039-8subject
Has Abstractpub_date
2016-06-01 00:00:00pages
725-30issue
6eissn
0031-6970issn
1432-1041pii
10.1007/s00228-016-2039-8journal_volume
72pub_type
杂志文章,随机对照试验abstract：:The number of marketed non-steroidal anti-inflammatory agents varies widely from one European country to another, partly as a consequence of differing regulatory policies. During a four-year period, nine of 18 applications to market such drugs in the Netherlands failed; the remaining nine compounds were all licenced; ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00558371
更新日期：1981-01-01 00:00:00
abstract：BACKGROUND:Spontaneous reporting of adverse drug reactions (ADRs) is one approach to increasing our knowledge on the risks of drugs in clinical practice. Under-reporting is a shortcoming of this system. OBJECTIVES:To evaluate if repeated e-mails with attachments on ADR information can affect (1) the reporting of ADRs ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-008-0603-6
更新日期：2009-05-01 00:00:00
abstract：:The pharmacokinetics and metabolism of quinidine were investigated in extensive and poor metabolisers of sparteine. No differences in plasma clearance, terminal half life, volume of distribution or cumulative urinary excretion of quinidine, 3-hydroxyquinidine and quinidine-N-oxide were observed between phenotypes. Thu...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00870989
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abstract：:The effects of metolazone on the protein binding of glibenclamide were studied. It was found that increasing metolazone concentrations up to 100 ng/ml had no significant effect on the protein binding of glibenclamide studied at 10 micrograms/ml. Metolazone is unlikely to cause a clinically significant increase in the ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00314813
更新日期：1990-01-01 00:00:00
abstract：OBJECTIVE:To quantify the relation between local and systemic magnitudes of effects of inhaled formoterol and salbutamol. METHODS:Twenty-eight stable asthmatic patients completed this double-blind, randomised crossover study. Pre-drug administration FEV1 (mean 2.08 L) was 49-93% of predicted and reversibility 16-82% a...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：2002-07-01 00:00:00
abstract：:Milrinone, a new, nonglycosidic inotropic agent with peripheral vasodilating properties, was given as a single oral 5 mg dose to 7 healthy subjects, 7 patients with moderate renal impairment (CRI I, creatinine clearance 30-63 ml/min) and 7 patients with severe renal impairment had hypertension. The mean urinary recove...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00635891
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abstract：OBJECTIVES:Designing a safe medication process requires the ability to model its reliability using methods such as probabilistic risk assessment (PRA). However, lack of data, especially on human-error probabilities (HEPs), limits its use. To assess whether small-scale simulations could help generate HEP data, a pilot s...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-007-0319-z
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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：2010-04-01 00:00:00
abstract：PURPOSE:A population pharmacokinetic analysis was performed to define domperidone pharmacokinetic parameters in preterm neonates, as no pharmacokinetic data are available in this population. METHODS:An oral domperidone solution was administered (0.75 mg/kg per day) in 32 preterm neonates (64 samples). Domperidone plas...
journal_title：European journal of clinical pharmacology
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doi：10.1007/s00228-008-0535-1
更新日期：2008-12-01 00:00:00
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journal_title：European journal of clinical pharmacology
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doi：10.1007/s00228-004-0732-5
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journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
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journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-013-1474-z
更新日期：2013-07-01 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
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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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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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journal_title：European journal of clinical pharmacology
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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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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/BF00315392
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abstract：:We have given 12 healthy subjects the H1-antihistamine ebastine (20 mg) or placebo in a double-blind, crossover study for one week each. The subjects were tested for drug effects on Day 6 of each period, and for interactions of ebastine with ethanol (0.8 g.kg-1) on Day 7. On both days, the testing runs were done at ba...
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：1992-01-01 00:00:00
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journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050199
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abstract：:The pharmacokinetic profiles of transdermal timolol 6 and 24 mg (as 5 and 20% w/v patches) was studied in four healthy young volunteers. To assess its bioavailability, the pharmacokinetics of an IV infusion of timolol maleate 5 mg was also determined in the same subjects. When the 20% (w/v) timolol patch was applied, ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
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更新日期：1993-01-01 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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journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
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更新日期：1987-01-01 00:00:00
abstract：OBJECTIVE:The analgesic efficacy of intravenous doses of acetaminophen (paracetamol) 0.5 g, 1 g and 2 g (administered as propacetamol) was assessed in 11 healthy subjects in a randomised, double-blind, placebo-controlled crossover study. The antinociceptive effect was assessed over 8 h by measurement of the nociceptive...
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：:Serotonin (5-HT) stimulates prolactin release. In the present study the ability of dexfenfluramine to increase serum prolactin was used as an index of central 5-HT function after acute and chronic pretreatment of volunteers with fluoxetine. Following a single-blind, random design, on each experimental day each volunte...
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：1994-01-01 00:00:00
abstract：:Twenty three patients with essential hypertension who were uncontrolled on diuretic and/or beta-receptor antagonist therapy were treated additionally with the vasodilator, pinacidil, in an open study. Significant reduction in mean blood pressure was achieved. Supine and erect systolic and diastolic blood pressure fell...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00543335
更新日期：1985-01-01 00:00:00
