The glucokinase activator AZD6370 decreases fasting and postprandial glucose in type 2 diabetes mellitus patients with effects influenced by dosing regimen and food.

Aims: To investigate the pharmacodynamics, pharmacokinetics and safety of the glucokinase activator AZD6370 after 1 day of administration under fed and fasted conditions in patients with type 2 diabetes mellitus (T2DM).

Methods: This was a two-part study. In Part A, patients received a single oral dose of AZD6370 (20, 60 or 180 mg) or placebo in the fasted or fed states (both n=8).

Tolerability, pharmacokinetics, and pharmacodynamics of the glucokinase activator AZD1656, after single ascending doses in healthy subjects during euglycemic clamp.

Objectives: AZD1656 is a novel glucokinase activator with a postulated dual mechanism of action by activating glucokinase in both the pancreas and the liver, and with the potential to deliver effective glucose-lowering in Type 2 diabetes mellitus. Here, we present the tolerability, pharmacokinetics and pharmacodynamics of AZD1656 in two single-blind, randomized, placebo-controlled studies, one with Western and the other with Japanese healthy adult male subjects.

Methods: Both studies evaluated oral single ascending doses of AZD1656 of up to 180 mg, administered during euglycemic clamp conditions to explore a wide dose range without risking hypoglycemia.

Population pharmacokinetics of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, in atrial fibrillation patients receiving long-term anticoagulation therapy.

Background: Ximelagatran is an oral direct thrombin inhibitor for the prevention of thromboembolic disease. After oral administration, ximelagatran is rapidly absorbed and bioconverted to its active form, melagatran.

Objective: To characterise the pharmacokinetics of melagatran in patients with nonvalvular atrial fibrillation (NVAF) receiving long-term treatment for prevention of stroke and systemic embolic events.

No pharmacokinetic or pharmacodynamic interaction between digoxin and the oral direct thrombin inhibitor ximelagatran in healthy volunteers.

The interaction potential of digoxin and ximelagatran, an oral direct thrombin inhibitor being developed for the prevention and treatment of thromboembolic disease, was investigated in this randomized, double-blind, 2-way crossover study. On 2 separate occasions, healthy female and male volunteers (n = 16) received ximelagatran 36 mg or placebo twice daily for 8 days separated by a 4- to 14-day washout period. All volunteers received a single oral dose of digoxin 0.

Consistent pharmacokinetics of the oral direct thrombin inhibitor ximelagatran in patients with nonvalvular atrial fibrillation and in healthy subjects.

Objective: To investigate the influence of nonvalvular atrial fibrillation (NVAF) on the pharmacokinetic (PK) properties of the oral direct thrombin inhibitor ximelagatran and its active form, melagatran.

Methods: In an open study, 12 patients with persistent NVAF and 12 age- and gender-matched, healthy control subjects received a 10-min intravenous (i.v.

No influence of obesity on the pharmacokinetics and pharmacodynamics of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran.

Background: Ximelagatran, 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.

Effects of ximelagatran, an oral direct thrombin inhibitor, r-hirudin and enoxaparin on thrombin generation and platelet activation in healthy male subjects.

Objectives: The effects of ximelagatran, an oral direct thrombin inhibitor (DTI), recombinant hirudin (r-hirudin) and enoxaparin on thrombin generation and platelet activation were studied in humans.

Background: Recombinant hirudin (parenteral DTI) and enoxaparin (low molecular weight heparin) have been demonstrated to be clinically effective in acute coronary syndromes. Ximelagatran is currently under investigation for the prevention and treatment of thromboembolism.

The usefulness of sugar surfactants as solubilizing agents in parenteral formulations.

The usefulness of sugar surfactants as solubilizing agents was assessed and compared to commercial polyoxyethylene-based surfactants. The sugar surfactants examined comprised of monosaccharides or disaccharides with alkyl chains ranging from C(8) to C(12). Each surfactant was investigated with respect to solubilization capacity for felodipine and haemolytic activity.