Clinical pharmacokinetics and pharmacodynamics of insulin glulisine.

Insulin glulisine injection [3(B)-Lys, 29(B)-Glu-human insulin] is the newest human insulin analogue product for the control of mealtime blood sugar. As with insulin aspart and insulin lispro products, the insulin glulisine product displays faster absorption and onset of action, with a shorter duration of action than that of regular human insulin. The modifications of the amino acid sequence at positions 3 and 29 in the B chain of human insulin simultaneously provide stability to the molecular structure and render the insulin glulisine molecule less likely to self-associate, compared with human insulin, while still allowing the formation of dimers at pharmaceutical concentrations.

Advantage of premeal-injected insulin glulisine compared with regular human insulin in subjects with type 1 diabetes.

Objective: Insulin glulisine, a rapid-acting insulin analog, provides prandial insulin replacement. In this study, we compared postprandial blood glucose control after pre- and postmeal insulin glulisine with regular human insulin (RHI).

Research Design And Methods: In a single-dose, randomized, four-way complete cross-over study, subjects received standardized, 15-min meals, covered by subcutaneous injections of either insulin glulisine (immediately premeal or 15 min postmeal; 0.

Anticoagulant and anti-platelet effects are maintained following coadministration of otamixaban, a direct factor Xa inhibitor, and acetylsalicylic acid.

The pharmacokinetics, pharmacodynamics and safety of the direct factor Xa inhibitor, otamixaban, with and without concomitant acetylsalicylic acid (ASA) were investigated in healthy volunteers. The study was a double-blind, placebo-controlled 3-way crossover study. Sixty-eight male volunteers in total were randomised to otamixaban, ASA, or otamixaban with ASA.

The effect of smoking cessation and subsequent resumption on absorption of inhaled insulin.

Objective: To assess the absorption profile of inhaled insulin in healthy, actively smoking subjects at baseline, after smoking cessation, and after smoking resumption and compare it with nonsmoking subjects.

Research Design And Methods: Insulin pharmacokinetics and glucodynamics were measured in 20 male smoking subjects (10-20 cigarettes/day) and 10 matched nonsmoking subjects after receiving inhaled insulin (1 mg) or the approximate subcutaneous insulin equivalent (3 units) in a randomized cross-over fashion. All smokers then received inhaled insulin 12 h, 3 days, and 7 days into a smoking cessation period.

Pharmacokinetic/pharmacodynamic relationships for otamixaban, a direct factor Xa inhibitor, in healthy subjects.

Direct pharmacokinetic/pharmacodynamic relationships for otamixaban were investigated after rising doses in healthy subjects using mixed-effect modeling. Activated partial thromboplastin time, prothrombin time, dilute prothrombin time, and Russell's viper venom-induced clotting time (RVVT) related linearly, whereas Heptest clotting time (HCT) followed a sigmoidal E(max) model. The pharmacokinetic/pharmacodynamic response (slope) and their corresponding interindividual variability (seconds per ng/mL, [% coefficient of variation]) were 0.

Pharmacokinetics of otamixaban, a direct factor Xa inhibitor, in healthy male subjects: pharmacokinetic model development for phase 2/3 simulation of exposure.

The pharmacokinetics of otamixaban was investigated in healthy male subjects over a wide range of intravenous doses, with duration of administration varying between 1-minute infusions (bolus dose) and 24-hour infusions, using noncompartmental and multicompartmental methods. A global compartmental analysis (2 and 3 compartments) generated a single set of pharmacokinetic parameters, regardless of infusion rate and duration, and took into account the 30% decrease in clearance and volume of distribution observed over the dose range. The 2-compartment model was retained to predict bolus plus 3-hour-infusion doses of otamixaban for future phase (2/3) studies.

Pharmacokinetics, prandial glucose control, and safety of insulin glulisine in children and adolescents with type 1 diabetes.

Objective: The aim of this study was to investigate the pharmacokinetics, postprandial blood glucose excursions, and safety of insulin glulisine as compared with regular human insulin (RHI), both administered immediately before meals in pediatric patients with type 1 diabetes.

Research Design And Methods: A total of 10 children (aged 5-11 years) and 10 adolescents (aged 12-17 years) were enrolled in a randomized, single-center, single-dose, double-blind, cross-over study. The blood glucose of fasting patients was stabilized with intravenous insulin, following which patients received 0.