TABLE 4

Summary of pharmacokinetic parameters for MFM and PYR in cynomolgus monkeys (n = 3) after a single intravenous dose of MFM (3.9 mg/kg) with and without an intravenous dose of PYR (0.5 mg/kg)

AnalyteVariableMFM AloneWith PYRRatio (90% CI)
MFMAUC0-inf (µM·h)46.4 ± 9.0102 ± 2.3**2.23 (1.57–3.17)
Vss (l/kg)0.98 ± 0.160.88 ± 0.210.88 (0.45–1.73)
CL (ml/min/kg)11.2 ± 2.45.0 ± 0.1*0.45 (0.32–0.64)
% Urinary excretion of dose (0–48 hours)94.1 ± 8.4105 (79.8 and 130)aN.C.
CLR (ml/min/kg)10.7 ± 3.15.3 (3.9 and 6.7)aN.C.
T1/2 (hour)7.1 ± 1.313.9 ± 1.8**1.98 (1.74–2.25)
PYRCmax (nM)607 ± 14.7
AUC0-49hour (nM·h)11,300 ± 983
Vss (l/kg)4.0 ± 0.6
CL (ml/min/kg)2.4 ± 0.3
C49 hour (nM)82.9 ± 22.0
T1/2 (hour)20.9 ± 5.2
  • Data are shown as mean ± S.D. (n = 3 animals). The pharmacokinetic parameters were determined as indicated under Materials and Methods. PYR was intravenously dosed 60 min before MFM.

  • a Cage malfunction prevented urine collection from one animal in the coadministration treatment group (N = 2).

  • * P < 0.05 and **P < 0.01 compared with values for the in the absence of PYR; N.C., not calculated.