Pharmacokinetics of a new proton pump inhibitor, YJA-20379-8, after intravenous and oral administration to spontaneously hypertensive rats and DOCA-salt-induced hypertensive rats.
The purpose of this study was to investigate the causes for the differences observed in the pharmacokinetics of YJA-20379-8 in 16-week-old spontaneously hypertensive rats (SHRs). To see if the hereditary characteristics of SHRs was the cause, 20 mg/kg of the drug was intravenously infused over 15 min and 50 mg/kg of the drug was orally administered to 6-week-old SHRs and 16-week-old SHRs and their age-matched control Kyoto-Wistar (KW) rats. Also to see if the hypertensive status itself was the cause, the same doses were administered to 16-week-old deoxycorticosterone acetate (DOCA) salt-induced hypertensive rats (DOCA-salt rats) and their age-matched control Sprague-Dawley rats. The areas under the plasma concentration-time curve from time zero to time infinity (for intravenous study) and to the last sampling time in plasma (for oral study) were significantly smaller after both intravenous and oral administration, and the total body clearances of the drug were significantly faster after intravenous administration to 6-week-old SHRs, 16-week-old SHRs, and 16-week-old DOCA-salt rats than those in their respective age-matched control rats. The above pharmacokinetic parameter changes in 16-week-old SHRs were due to both hereditary characteristic of SHRs and the hypertensive status itself.
Kim
H J
HJ
College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong. Kwanak-Gu, Seoul 151-742, Republic of Korea.
Han
K S
KS
Kim
Y G
YG
Chung
Y K
YK
Chang
M S
MS
Lee
M G
MG
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003900:Desoxycorticosterone; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D009287:Naphthyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D054328:Proton Pump Inhibitors; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
C114511:3-butyryl-4-(5R-methylbenzylamino)-8-ethoxy-1,7-naphthyridine; D004791:Enzyme Inhibitors; D009287:Naphthyridines; D054328:Proton Pump Inhibitors; D003900:Desoxycorticosterone