Table 2

Parameters of simultaneous PK and PD modeling of pimo (enantiomer concentration versus LVESD) in eight normal healthy volunteers

ParameterUnitPlasma (Mean ± S.E.)Red Blood Cell (Mean ± S.E.)
(+)-pimo(−)-pimo(+)-pimo(−)-pimo
Oral study
 K e0 2-a 1/h0.33  ± 0.070.33  ± 0.060.35  ± 0.070.30  ± 0.07
 n2.43  ± 0.572.37  ± 0.572.62  ± 0.852.23  ± 0.51
 C e50 ng/ml6.54  ± 1.356.64  ± 1.3534.62  ± 6.3039.01  ± 6.38
 Emax cm2.60  ± 0.512.30  ± 0.132.16  ± 0.421.75  ± 0.34
 E0 cm3.36  ± 0.133.36  ± 0.133.35  ± 0.123.39  ± 0.11
 E0(obs) 2-b cm3.45  ± 0.113.45  ± 0.113.45  ± 0.113.45  ± 0.11
 Tmax(e) 2-c h3.51  ± 0.393.58  ± 0.393.56  ± 0.383.86  ± 0.41
 Tmax 2-d h1.23  ± 0.181.24  ± 0.171.14  ± 0.191.15  ± 0.19
 ΔTmax 2-e h2.28  ± 0.282.34  ± 0.272.42  ± 0.322.71  ± 0.38
i.v. study
 K e0 1/h0.18  ± 0.030.19  ± 0.042-150 0.17  ± 0.010.19  ± 0.02
 n4.38  ± 1.024.92  ± 1.335.33  ± 1.216.32  ± 1.272-150
 C e50 ng/ml5.54  ± 1.105.54  ± 1.3027.79  ± 6.4837.31  ± 6.12
 Emax cm2.28  ± 0.662.17  ± 0.582.71  ± 0.711.51  ± 0.38
 E0 cm3.20  ± 0.093.20  ± 0.083.19  ± 0.093.18  ± 0.09
 E0(obs) cm3.22  ± 0.093.22  ± 0.093.22  ± 0.093.22  ± 0.09
 Tmax(e) h3.07  ± 0.253.45  ± 0.553.12  ± 0.363.09  ± 0.25

  • ↵2-a Elimination rate constant of the hypothetical effect compartment.

  • ↵2-b Observed baseline value of LVESD.

  • ↵2-c Time to reach peak effect.

  • ↵2-d Time to reach peak concentration.

  • ↵2-e Lag time between Tmax(e) and Tmax.

  • ↵2-150  p < .05 in comparison between oral and i.v. studies.