TABLE 4

Comparison of simulated human pharmacokinetic parameters using various scaling methodologies for clearance and Vdss and pharmacokinetics of CJ-13,610 after a 30-mg single oral dose to healthy male subjects

All pharmacokinetic simulations were conducted using WinNonlin, and an absorption rate constant (ka) of 0.83 h−1 (estimated by modeling rat oral pharmacokinetic data) was used. High oral bioavailability was also assumed. n = 4.

Scaling MethodologyClearanceVdssaAUC0–∞Cmaxt1/2
ml/min/kgl/kgngh/mlng/mlh
Human liver microsomes (Vdss scaled from rat)3.6b6.718025121.7
Human liver microsomes (Vdss scaled from dog)3.6b3.218029710.4
Scaled from rat pharmacokinetics5.3c6.712224814.7
Scaled from dog pharmacokinetics3.2c3.220149811.6
Single oral dose (30 mg)1970 (220)144 (34)13.4 (2.1)
  • a Predicted Vdss in human from either rat or dog using eq. 8.

  • b Predicted clearance in human using eq. 1.

  • c Predicted clearance in human using eq. 7.