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 (i.v.) administration to rats (10-50 mg/kg) and rabbits (10-50 mg/kg), and oral administration to rats (200 and 500 mg/kg). The stability and blood partition between plasma and blood cells were also investigated. After i.v. administration of YJA-20379-1, 10-50 mg/kg, to rats, the pharmacokinetic 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 increasing doses (73.4 +/- 28.5 and 130 +/- 100 micrograms min/ml for 200 and 500 mg/kg, respectively). The extent of absorption after oral administration (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 extensive first-pass metabolism. YJA-20379-1 was unstable in pH solutions of 2-5, 12, and 13, very unstable in pH solutions of 1 and 14, however, stable in pH solutions of 6-11. YJA-20379-1 reached equilibrium rapidly between plasma and blood cells of rabbit blood at 1-5 micrograms/ml, an the mean blood cells/plasma concentration ratio was 5.24 +/- 1.21.