TABLE 2

Parameter estimates from PK/PD modeling

Parameter estimate ± S.E. from nonlinear regression analysis of pooled mdr1a(+/+) mouse data.


Parameter

Alfentanil

Fentanyl

Loperamide

Meperidine

Methadone

Morphine

Sufentanil
Ka (min-1) 0.35 ± 0.03 0.07 ± 0.07 0.063 ± 0.015 0.39 ± 0.18 0.55 ± 0.13 0.27 ± 0.04 0.32 ± 0.12
Cl (ml · min-1 · kg-1) 82 ± 3 90 ± 40 58 ± 7 190 ± 40 127 ± 12 95 ± 5 19 ± 3
Vc (ml · kg-1) 1000 ± 60 3000 ± 3000 32,000 ± 3000 6100 ± 1200 8800 ± 600 2900 ± 180 400 ± 80
Cld (ml · min-1 · kg-1) 40 ± 30
Vp (ml · kg-1) 5000 ± 13,000
Clup (ml · min-1 · kg-1) 4 ± 3 8 ± 3 0.04 ± 0.06 100 ± 40 27 ± 4 9.5 ± 0.5 37 ± 14
Clefflux (ml · min-1 · kg-1) 22 ± 17 3.4 ± 1.4 0.3 ± 0.5 8 ± 4 5.1 ± 0.9 1.9 ± 1.4 12 ± 5
EC50 (ng/g) 9.2 ± 1.7 6.4 ± 1.1 100 ± 6 2200 ± 110 510 ± 60 38 ± 4 1.0 ± 0.2
γ 1.8 ± 0.4 1.4 ± 0.3 2.7 ± 0.5 7.8 ± 4.2 3.7 ± 1.1 2.3 ± 0.5 2.5 ± 1.3
K p,brain 0.195 ± 0.0087 2.3 ± 0.2 0.115 ± 0.014 6.8 ± 0.5 3.3 ± 0.2 1.1 ± 0.6 2.1 ± 0.3
keq (min-1) 0.64 ± 0.09 0.14 ± 0.04 0.025 ± 0.010 0.13 ± 0.03 0.073 ± 0.014 0.009 ± 0.006 0.16 ± 0.06
t1/2eq,brain (min)a
1.08 ± 0.16
4.9 ± 1.3
27 ± 11
5.4 ± 1.1
9.6 ± 1.8
74 ± 45
4.3 ± 1.6
  • a t1/2eq,brain were calculated from 0.693/keq,brain.