Table 1

Permeabilities, fraction metabolized, metabolite formation, metabolite excretion, and extraction ratios for K77 and midazolam across rat ileum

Condition1-aPlumen × 104Pblood × 104Fraction Metabolized1-bCumulative Amount of Drug in Blood or Plasma1-cCumulative Amount of Metabolites1-dER1-e
in Perfusatein Blood or Plasma
cm/s pmol/cm 2 pmol/cm2
K77
 100 μM0.8 ± 0.40.04 ± 0.020.95 ± 0.02669 ± 3731,430 ± 79036 ± 17*0.60 ± 0.01
 50 μM1.1 ± 0.70.05 ± 0.030.95 ± 0.03494 ± 264794 ± 4143 ± 50.49 ± 0.12
 50 μM + 5 μM GG9181.0 ± 0.20.15 ± 0.07*0.85 ± 0.04*1,360 ± 6501,210 ± 32540 ± 13*0.37 ± 0.03
Midazolam
 100 μM0.9 ± 0.40.8 ± 0.1−0.03 ± 0.4215,000 ± 1740*37 ± 7150 ± 80.010 ± 0.001
 50 μM1.4 ± 0.41.1 ± 0.30.19 ± 0.146,350 ± 245020 ± 1255 ± 90.011 ± 0.003
 50 μM + 5 μM GG9181.5 ± 0.21.1 ± 0.10.27 ± 0.038,090 ± 74822 ± 7113 ± 680.014 ± 0.009

Data shown are the mean ± S.D. (n = 3).

  • 1-150 Significantly different compared to 50 μM dose for that compound (K77 or midazolam).

  • 1-a K77 data calculated at 60 min and midazolam data calculated at 40 min

  • 1-b Fraction of drug metabolized was calculated from eq. 4 using paired Pblood and Plumen data from individual animals.

  • 1-c K77 and its metabolites were extracted from blood, whereas midazolam and its metabolites were extracted from plasma.

  • 1-d Sum of N-desmethyl and N-oxide metabolites for K77 and sum of 1-OH and 4-OH metabolites for midazolam.

  • 1-e Extraction ratio calculated from eq. 5 using metabolite and parent data from individual animals.