Background: Sulfonylurea therapy allows a better metabolic control than insulin in patients with neonatal diabetes secondary to mutation in potassium channel. Its galenic form (tablets) is not suitable for children, as the dosage cant be easily modulated and as it induces large pharmacokinetics (PK) variations when administer to young children.
Objective and hypotheses: To measure relative biodisponibility of a new galenic form of glibenclamide and to assess its safety and tolerability.
Method: Open-label, cross over randomised phase 1 study in 18 healthy male subjects. Single oral administration, in fasted conditions of two new oral glibenclamide suspensions (0.83 ml of a 6 mg/ml suspension (S6) and 8.33 ml of a 0.6 mg/ml suspension (S0.6)) and of 5 mg of Daonil crushed tablet (DCT).
Results: When suspensions were administered, glibenclamide plasma concentrations peaked 0.5 h earlier than observed with a DCT (median value of 2.5 h post-dose vs 3.0 h post-dose). Mean plasma peak Cmax values were similar for the two suspensions (S6: 201.71±71.43 ng/ml and S0.6: 206.93±67.33 ng/ml), ~40% higher than the DCT one (148.34±46.74 ng/ml). Exposures were similar for the two suspension dosages (AUC0-∞ values: S6: 1120.9±400.5 ng.h/ml and S0.6: 1172.3±422.0 ng.h/ml), and superior to that observed after DCT administration. Relative bioavailability was 121.6% for the 0.6 mg/ml and 114.1% for the 6 mg/ml formulations when compared to the DCT. Elimination half-lives were similar for the two suspensions (close to 8 h) and a little shorter than that observed with DCT (10.45 h). No adverse events were reported.
Conclusion: Suspension of glibenclamide appears to be more suitable for use in paediatric patients as its dosage can be adjusted to patients needs with great precision more easily. PK studies reported it to be better absorbed than glibenclamide tablets. Tolerance and acceptability are being evaluated in patients with neonatal diabetes (ClinicalTrials.gov Identifier: NCT02375828).
01 Oct 2015 - 03 Oct 2015