Species | Route | Dosea | Cmax | Tmax | AUCtot | t1/2 | CLp | Vss | F |
---|---|---|---|---|---|---|---|---|---|
mg/kg | μg/ml | h | μg·h/ml | h | ml/min/kg | l/kg | % | ||
Rat | IA | 1 | 3.55 ± 0.42 | 4.6 ± 0.8 | 4.8 ± 0.6 | 1.6 ± 0.1 | |||
PO | 1 | 0.60 ± 0.46 | 1.7 ± 2.0 | 2.96 ± 0.73 | 84 ± 21 | ||||
Dog | IV | 6.6 | 76.4 ± 10.1 | 7.4 ± 1.2 | 1.5 ± 0.2 | 0.8 ± 0.1 | |||
PO | 6.6 | 10.7 ± 1.6 | 0.6 ± 0.4 | 63.6 ± 7.3 | 83 ± 2 | ||||
Monkey | IV | 6 | 17.1 ± 6.8 | 3.5 ± 1.9 | 6.4 ± 2.3 | 0.8 ± 0.2 | |||
PO | 6 | 1.54 ± 0.40 | 1.9 ± 1.8 | 4.27 ± 2.17 | 25 ± 2 | ||||
Humanb | PO | 50 mg | 0.55 ± 0.02 | 0.5 (0.5–0.75) | 2.43 ± 0.03 | 13.8 ± 9.4 | 4.9 ± 0.2c | d | d |
IA, intra-arterial; PO, oral; IV, intravenous.
↵a Dosing vehicle used in preclinical pharmacokinetic studies was polyethylene glycol 400/water/ethanol (45:45:10); in clinical study, the dose was administered as a pressed tablet.
↵b Urinary excretion of dapagliflozin (after an oral dose) in dogs was 3.4 ± 0.2%; in monkeys, 3.8 ± 0.3%; and in humans, 1.6 ± 0.8% of the total dose. Urinary excretion was not measured in rats.
↵c CL/F (observed).
↵d Vss and F were not calculated in humans because there were no IV data.