TABLE 1

Pharmacokinetic parameters of dapagliflozin in preclinical species after single intravenous or oral doses and in humans after single oral dose

SpeciesRouteDoseaCmaxTmaxAUCtott1/2CLpVssF
mg/kgμg/mlhμg·h/mlhml/min/kgl/kg%
RatIA13.55 ± 0.424.6 ± 0.84.8 ± 0.61.6 ± 0.1
PO10.60 ± 0.461.7 ± 2.02.96 ± 0.7384 ± 21
DogIV6.676.4 ± 10.17.4 ± 1.21.5 ± 0.20.8 ± 0.1
PO6.610.7 ± 1.60.6 ± 0.463.6 ± 7.383 ± 2
MonkeyIV617.1 ± 6.83.5 ± 1.96.4 ± 2.30.8 ± 0.2
PO61.54 ± 0.401.9 ± 1.84.27 ± 2.1725 ± 2
HumanbPO50 mg0.55 ± 0.020.5 (0.5–0.75)2.43 ± 0.0313.8 ± 9.44.9 ± 0.2cdd
  • 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.