Pharmacokinetics and pharmacodynamics of dapagliflozin in children and adolescents with type 2 diabetes mellitus

Aims: To evaluate the pharmacokinetic (PK)/pharmacodynamic (PD) and safety profile of dapagliflozin in paediatric patients aged 10-17 years with type 2 diabetes mellitus (T2DM). Methods: Patients were randomized to a single oral dose of dapagliflozin 2.5, 5 or 10mg. The PK characteristics for individual patients were derived by non-compartmental methods. Urinary glucose excretion (UGE), fasting plasma glucose (FPG) and ease of swallowing were also evaluated. Results: A total of 24 patients with a mean (range) body weight of 99.7 (61.5-169.5) kg received dapagliflozin. Dapagliflozin was rapidly absorbed after oral administration (median time to maximum plasma concentration similar to 1.5 h) and systemic exposures to dapagliflozin and its 3-O-glucuronide metabolite appeared dose-proportional. The mean 24-h UGE increased in a dose-related manner (52.8, 62.4 and 89.0 g for the 2.5, 5 and 10 mg groups, respectively). Mean FPG concentrations were lower for all dose groups on day 2 (6.9, 6.2 and 6.8 mmol/l for 2.5, 5 and 10 mg groups, respectively) than they were predose on day 1 (9.5, 8.5 and 8.2 mmol/l for 2.5, 5 and 10 mg groups, respectively). Six patients (25%) experienced >= 1 adverse event (AE), however, there was no dose-related pattern. All AEs occurred only once and most were mild in intensity. Nearly all patients (n= 23; 95.8%) reported easy swallowing of the dapagliflozin tablets. Conclusions: Dapagliflozin was well tolerated in this paediatric population, with no significant safety findings. PK/PD characteristics were similar to those observed in adults with T2DM, thereby supporting the hypothesis that the same dapagliflozin dosage as that used in adults can be evaluated in future phase III paediatric studies.