Complications in the estimation of hepatic blood flow in vivo by pharmacokinetic parameters. The area under the curve after the concomitant intravenous and intraperitoneal (or intraportal) administration of acetaminophen in the rat.
Hepatic blood flow can be estimated from the area under the blood or plasma concentration-time curve of a drug following an intravenous dose and either an oral or intraperitoneal dose. The validity of the method depends on several factors which alter the area under the curve, that is, hemodynamic interactions due to the drug or its metabolites, the use of plasma concentration as opposed to blood concentration data, incomplete absorption on oral or intraperitoneal administration, enterohepatic recycling of the drug or its metabolite, and the presence of extrahepatic metabolism. The validity of the method was tested in rats with tracer doses of acetaminophen. After the simultaneous administration of an iv dose of 14C-acetaminophen and an intraportal dose of 3H-acetaminophen to rats, the availability after the first-pass hepatic extraction of acetaminophen in rats was 0.56 +/- 0.05. Hepatic blood flow estimated by the area under the curve for the respective routes of administration was 78.1 +/- 16.1 ml/min/kg. However, after the simultaneous administration of an iv tracer dose of 14C-acetaminophen and an ip dose of 3H-acetaminophen, the apparent availabilities calculated from the areas under the curve were highly variable and tended to be greater (0.73 +/- 0.11). Thus the estimates of the hepatic blood flow also tended to be higher (159 +/- 65 ml/min/kg).
Complications in the estimation of hepatic blood flow in vivo by pharmacokinetic parameters. The area under the curve after the concomitant intravenous and intraperitoneal (or intraportal) administration of acetaminophen in the rat. Hepatic blood flow can be estimated from the area under the blood or plasma concentration-time curve of a drug following an intravenous dose and either an oral or intraperitoneal dose. The validity of the method depends on several factors which alter the area under the curve, that is, hemodynamic interactions due to the drug or its metabolites, the use of plasma concentration as opposed to blood concentration data, incomplete absorption on oral or intraperitoneal administration, enterohepatic recycling of the drug or its metabolite, and the presence of extrahepatic metabolism. The validity of the method was tested in rats with tracer doses of acetaminophen. After the simultaneous administration of an iv dose of 14C-acetaminophen and an intraportal dose of 3H-acetaminophen to rats, the availability after the first-pass hepatic extraction of acetaminophen in rats was 0.56 +/- 0.05. Hepatic blood flow estimated by the area under the curve for the respective routes of administration was 78.1 +/- 16.1 ml/min/kg. However, after the simultaneous administration of an iv tracer dose of 14C-acetaminophen and an ip dose of 3H-acetaminophen, the apparent availabilities calculated from the areas under the curve were highly variable and tended to be greater (0.73 +/- 0.11). Thus the estimates of the hepatic blood flow also tended to be higher (159 +/- 65 ml/min/kg).