STABILITY, BLOOD PARTITION, AND PHARMACOKINETICS OF A NEW REVERSIBLE PROTON PUMP INHIBITOR, YJA-20379-1

The pharmacokinetics of YJA-20379-1 were evaluated after intravenous ( iv) administration to rats (10-50 mg/kg) and rabbits (10-50 mg/kg), an d oral administration to rats (200 and 500 mg/kg). The stability and b lood partition between plasma and blood cells were also investigated. After iv administration of YJA-20379-1, 10-50 mg/kg, to rats, the phar macokinetic parameters of YJA-20379-1 were dose-independent, however, they were dose-dependent in rabbits. After oral administration of YJA- 20379-1 to rats, the AUC of YJA-20379-1 seemed to increase with increa sing doses (73.4 +/- 28.5 and 130 +/- 100 mu g min/ml for 200 and 500 mg/kg, respectively). The extent of absorption after oral administrati on (F) was 6.47 and 4.74% for 200 and 500 mg/kg, respectively. The low F values were not due to incomplete absorption and could be due to ex tensive first-pass metabolism. YJA-20379-1 was unstable in pH solution s of 2-5, 12, and 13, very unstable in pH solutions of 1 and 14, howev er, stable in pH solutions of 6-11. YJA-20379-1 reached equilibrium ra pidly between plasma and blood cells of rabbit blood at 1-5 mu g/ml, a nd the mean blood cells/plasma concentration ratio was 5.24 +/- 1.21.