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.
Kim
S H
SH
College of Pharmacy, Seoul National University, South Korea.
Han
K S
KS
Choi
W S
WS
Chang
M S
MS
Lee
M G
MG
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D052160:Benzothiazoles; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000502:physiology; D008297:Male; D054328:Proton Pump Inhibitors; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*
D052160:Benzothiazoles; D007093:Imidazoles; D054328:Proton Pump Inhibitors; D013844:Thiazoles; C110270:YJA 20379-1