TABLE 1.

Spiramycin recovery in perfusate and bile and pharmacokinetic parameter estimates governing spiramycin disposition in single-pass perfused livers from B6, Mrp2KO, and BcrpKO micea

ParameterB6Mrp2KOBcrpKO
Spiramycin recovery (% of liver content at end of infusion)
    Perfusate
        Vehicle32.5 ± 4.829.5 ± 6.028.1 ± 5.6
        GW91834.1 ± 4.524.0 ± 4.825.2 ± 2.3
    Bileb,c
        Vehicle9.15 ± 4.151.21 ± 1.2314.1 ± 2.0
        GW9184.36 ± 0.480.58 ± 0.268.28 ± 0.80
Pharmacokinetic parameter estimates
    CLup (ml/min)
        Vehicle4.63 ± 0.375.15 ± 0.234.55 ± 0.44
        GW9184.64 ± 0.204.70 ± 0.145.03 ± 0.05
    Kps (min−1)c
        Vehicle0.488 ± 0.1780.420 ± 0.0790.453 ± 0.047
        GW9180.317 ± 0.0410.373 ± 0.0340.311 ± 0.014
    K12 (min−1)
        Vehicle0.0427 ± 0.01510.0501 ± 0.03170.0441 ± 0.0200
        GW9180.0240 ± 0.01100.0410 ± 0.00800.0209 ± 0.0040
    K21 (min−1)
        Vehicle0.1021 ± 0.03800.1434 ± 0.12610.1261 ± 0.0431
        GW9180.1012 ± 0.04070.0679 ± 0.02400.0933 ± 0.0100
    Kb(min−1)b,c
        Vehicle0.0124 ± 0.00960.0013 ± 0.00090.0270 ± 0.0153
        GW9180.0106 ± 0.00110.0004 ± 0.00010.0183 ± 0.0054
    K13 (min−1)
        Vehicle0.1066 ± 0.06180.2064 ± 0.08940.1669 ± 0.0781
        GW9180.1457 ± 0.02530.2123 ± 0.06740.2021 ± 0.0113
    K31 (min−1)
        Vehicle0.0009 ± 0.0001<0.00010.0022 ± 0.0013
        GW9180.0007 ± 0.0012<0.00010.0007 ± 0.0002
  • a Values are mean ± SD (n = 3 per group).

  • b P < 0.05, among mouse groups.

  • c P < 0.05, GW918 vs vehicle.