Possibility of partial absorption of nicardipine by routes other than the hepato-portal system after oral administration in rats.
The systemic availability of nicardipine after different routes of administration has been examined in rats, with particular attention to differentiating oral absorption from intestinal and hepatic metabolism. The quantities of nicardipine and its metabolite were determined by capillary column gas chromatography. A linear relationship was shown between the hepatic first-pass effect and dose after hepato-portal administration of nicardipine; the hepatic first-pass effect was calculated to be approximately 80%. However, the availability after oral and rectal administration was found to be more than twice that observed after hepato-portal administration. Partial avoidance of the hepatic first-pass effect after oral and rectal administration are estimated to be 37.3% and 35.2%, respectively, assuming that all absorbed molecules pass through the liver. These findings suggest that the absorption of nicardipine after oral administration also occurs by routes other than the hepato-portal system.
School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
J
J
Mizumura
N
N
Watari
S
S
Higuchi
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D019540:Area Under Curve; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism*; D008297:Male; D009529:Nicardipine / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D011169:Portal Vein; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics
D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D009529:Nicardipine