Pharmacokinetics of a new proton pump inhibitor, YJA-20379-8, in rats with 48-hour water deprivation.
The pharmacokinetics of YJA-20379-8 after the intravenous, 20 mg/kg, and oral, 50 mg/kg, administration of the drug, and tissue distribution of YJA-20379-8 after intravenous administration of the drug, 20 mg/kg, to control and 48-h water-deprived rats were reported. After 15-min intravenous infusion of YJA-20379-8, the drug was not detected in urine and less than 0.5% of intravenous dose of the drug was excreted in bile, suggesting that YJA-20379-8 is essentially completely metabolized in rats. Therefore, the CL (clearance) of YJA-20379-8 represents the CLNR (metabolic clearance) of the drug in rats. After oral administration of YJA-20379-8, the F values were low; the values were 21.2 and 19.4% for control and water-deprived rats, respectively. The values were considerably low considering that 93.4 and 84.6% orally administrated YJA-20379-8 were absorbed from rat GI tract of control and water-deprived rats, respectively. This could be due to considerable first-pass (hepatic, gastric, and intestinal) effects. Recently, it was found that gastric and intestinal first-pass effects of YJA-20379-8 were considerable in rats. The amounts of YJA-20379-8 in small intestine, brain, lung, stomach, and kidney increased significantly in water-deprived rats. However, the T/P ratios were comparable (not significantly different) for both groups of rats, indicating that tissue distribution of the drug was not affected by water deprivation.
Kim
H J
HJ
College of Pharmacy, Seoul National University, South Korea.
Han
K S
KS
Chung
Y K
YK
Chang
M S
MS
Lee
M G
MG
D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D009287:Naphthyridines / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D054328:Proton Pump Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014868:Water Deprivation
C114511:3-butyryl-4-(5R-methylbenzylamino)-8-ethoxy-1,7-naphthyridine; D000897:Anti-Ulcer Agents; D009287:Naphthyridines; D054328:Proton Pump Inhibitors