Trial reportClinical pharmacokinetics2003
No influence of obesity on the pharmacokinetics and pharmacodynamics of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran.
Trial report in Clinical pharmacokinetics, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 61 citations in OpenAlex.
- Weight-based dosing in medication use: what should we know?Patient preference and adherence · 2016Review
- Ximelagatran: direct thrombin inhibitor.Vascular health and risk management · 2006Review
- Postoperative Melagatran/Ximelagatran for the Prevention of Venous Thromboembolism following Major Elective Orthopaedic Surgery : Effects of Timing of First Dose and Risk Factors for Thromboembolism and Bleeding Complications on Efficacy and Safety.Clinical drug investigation · 2005Article
- No influence of food on the pharmacokinetics, pharmacodynamics or tolerability of the 24mg and 36mg oral tablet formulations of ximelagatran.Clinical drug investigation · 2005Article
- Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol.Clinical pharmacokinetics · 2005Review
- New approaches to anticoagulation in atrial fibrillation.Current cardiology reports · 2004Review
- Anticoagulation for non-valvular atrial aibrillation - towards a new beginning with ximelagatran.Current controlled trials in cardiovascular medicine · 2004Article
- Review
- Oral direct thrombin inhibition: an effective and novel approach for venous thromboembolism.Drugs · 2004Review
- Review
- A review of the clinical uses of ximelagatran in thrombosis syndromes.Journal of thrombosis and thrombolysis · 2003Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundXimelagatran, an oral direct thrombin inhibitor, is currently in clinical development for the prevention and treatment of thromboembolic disease. Following oral administration, ximelagatran undergoes rapid bioconversion to its active form, melagatran, via two minor intermediates. Obesity, defined as body mass index (BMI) >30 kg/m(2), is a recognised risk factor for thrombosis. There is potential for differences in the pharmacokinetics and pharmacodynamics of drugs administered to obese versus non-obese patients, and some drugs may require alternative administration strategies in obese patients.
objectiveTo investigate the effect of obesity on the pharmacokinetics and pharmacodynamics of melagatran after oral administration of ximelagatran. DESIGN AND
participantsThis was an open-label, single-dose, group-matched study in which obese subjects (BMI 32-39 kg/m(2); six male and six female; age 21-40 years) were matched by sex and age (+/-2 years) with non-obese subjects (BMI 21-26 kg/m(2); six male and six female; aged 21-39 years). Each subject received a single oral dose of ximelagatran 24mg. Blood samples for determination of plasma concentrations of melagatran and activated partial thromboplastin times (APTT; a marker of melagatran pharmacodynamics) were collected up to 12 hours after administration.
resultsThere were no statistically significant differences in the pharmacokinetic properties of melagatran between obese and non-obese subjects. Values of area under the melagatran plasma concentration-time curve, maximum plasma concentration (C(max)), time at which C(max) occurred and terminal elimination half-life were approximately 1 micromol. h/L, 0.2 micromol/L, 2 hours and 3 hours in both obese and non-obese subjects, respectively. In addition, there was no statistically significant difference between the obese and non-obese subjects in the amount of ximelagatran, melagatran or the minor intermediates ethyl-melagatran and melagatran hydroxyamidine excreted in urine. When relating the prolongation of APTT ratio to the square root of plasma concentration of melagatran and obesity status (no/yes), no statistically significant interaction between plasma concentration and obesity status was observed. Ximelagatran was well tolerated in both obese and non-obese subjects, and no bleeding events or serious adverse events occurred.
conclusionsNo differences in the pharmacokinetics or pharmacodynamics of melagatran were detected between obese and non-obese subjects after oral administration of ximelagatran, suggesting that dose adjustment of ximelagatran in obesity (BMI up to 39 kg/m(2)) is not necessary.
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