TABLE 1

Properties of compounds selected for study


Compound

In Vivo Rat CLint

In Vivo Human CLinta

Rat Hepatocyte CLint

Metabolites Quantified in Present Study

Cytochrome P450 Responsible for Metabolite Formation in Rat

pKab (Acid, Base, or Neutral)

Log Pb

fu in Rat Plasma
ml/min/SRW ml/min/kg μl/min/106 cells
TOL 1.5c 6 1.6d HTOL 2C 5.3 (A) 2.3 0.08c
WAR 2.5e 4.5 NA 4-OH WAR 2B
6-OH WAR 1A, 2B
7-OH WAR 2C, 2B 5.0 (A) 2.5 0.02f
8-OH WAR 1A, 2C
10-OH WAR 3A
PHE 39.4d 6.8 37d 4-OH PHE 2C 8.3 (A) 2.5 0.11-0.12g
NDZ NA 5.6 16h 4′-OH NDZ 2D NA (N) NA 0.034i
OXP 3A
7-EC 122j NA 26j 7-HC 1A, 2B NA (N) NA 0.22j
DZ 174k 30 82l 4′-OH DZ 2D 3.3 (N) 2.8 0.137i
NDZ 2C, 2D, 3A, 2B
TZ 3A, 2C
DEX 259m NA 105m DOR 2D, 3A 8.3 (B) 4.0 0.45m
MEM 3A
PROP
425n
745
1800o
NA
2D, 1A, 2C
9.5 (B)
1.3
0.031p
  • NA indicates data was not available in the literature; SRW, standard rat weight, 250 g.

  • a Human in vivo CLint values calculated from Benet et al. (1996) using the well stirred model (Houston, 1994)

  • b pKa and Log P values taken from Jack (1992)

  • c Matthew and Houston (1990)

  • d Ashforth et al. (1995)

  • e calculated from Hermans and Thijssen (1991)

  • f Yacobi and Levy (1977)

  • g Conard et al. (1971)

  • h A. Parker (personal communication, 2004)

  • i Klotz et al. (1976)

  • j Carlile et al. (1998)

  • k Zomorodi et al. (1995)

  • l Carlile (1994)

  • m Witherow and Houston (1999)

  • n Wood et al. (1979)

  • o Hallifax (1998)

  • p Gariépy et al. (1992)