Gastrointestinal absorption of a new reversible proton pump inhibitor, YJA-20379-8, and its pharmacokinetics after oral administration in acetic acid-induced gastric ulcer in rats.
The absorption of YJA-20379-8 (3-butyryl-4-[5-(R)-(+)-methylbenzylamino]-8-ethoxy-1,7-naphthyrid ine) from various rat gastrointestinal segments was evaluated using in-situ closed-loops. The pharmacokinetics of the drug were also evaluated after oral administration to rats with acetic acid-induced gastric ulcer (AIURs). The concentrations of YJA-20379-8 in the biological samples were analyzed by HPLC. The absorption of YJA-20379-8 from stomach and jejunum was fast, but approximately 50% of the drug was recovered from each segment at 24 h. The total areas under the plasma concentration-time curves from time zero to 24h (AUC(0-24h)) were 161, 392, 233, 365, and 226 microg min mL(-1) for stomach, duodenum, jejunum, ileum, and colon, respectively. After oral administration of the drug, the plasma concentrations and the resultant AUC (0- 12h) were not significantly different between control and AIURs. The detection limits of YJA-20379-8 in human plasma and urine were 50 and 100 ng mL(-1), respectively. The results suggest that modification of the oral dose of YJA-20379-8 may not be required in gastric ulcer patients if the present rat pharmacokinetic data could be extrapolated to man.
Chung
S Y
SY
College of Pharmacy, Seoul National University, Kwanak-Gu, Korea.
Han
K S
KS
Kim
H J
HJ
Kim
J
J
Chang
M S
MS
Lee
M G
MG
D019342:Acetic Acid; D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D007408:Intestinal Absorption; D008297:Male; D009287:Naphthyridines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*
C114511:3-butyryl-4-(5R-methylbenzylamino)-8-ethoxy-1,7-naphthyridine; D000897:Anti-Ulcer Agents; D009287:Naphthyridines; D019342:Acetic Acid