Pharmacokinetics and pharmacodynamics of canagliflozin in pediatric patients with type 2 diabetes.

ABSTRACT

OBJECTIVE: Canagliflozin, a sodium glucose cotransporter 2 inhibitor approved for the treatment of adults with type 2 diabetes (T2D), increases urinary glucose excretion (UGE) and lowers plasma glucose (PG) levels by reducing the renal threshold for glucose (RTG ). This study assessed the pharmacokinetics (PK) and pharmacodynamics (PD) of canagliflozin in pediatric T2D patients. METHODS: Patients, aged 10 to 17 years with mean weight 107.2 kg and body mass index 38.2 kg/m2 , underwent PK and PD assessments after receiving a single daily dose of canagliflozin 100 mg (n = 8) or 300 mg (n = 9) for 14 days. Data are presented as mean (SD). RESULTS: There were dose-dependent increases in the PK of canagliflozin 100 and 300 mg, with maximum plasma concentrations and areas under plasma concentration curves that were similar to the corresponding values in adults. Mean 24-hour RTG fell to 84.6 (13.8) mg/dL with canagliflozin 100 mg and to 69.1 (9.6) mg/dL with canagliflozin 300 mg; also consistent with reductions in RTG in adults. Mean 24-hour UGE increased from 5.3 (10.5) g at baseline to 74.1 (37.4) g with canagliflozin 100 mg and from 0.1 (0.04) g to 68.6 (26.5) g with canagliflozin 300 mg. Both doses were well tolerated and the tablets had acceptable taste, smell, and swallowability. CONCLUSIONS: In pediatric T2D patients, canagliflozin 100 and 300 mg had PK and PD characteristics similar to those in adults with T2D, which is likely due to the relative maturity and increased body weight of youth affected with this disorder.