Drug Absorption And Metabolism Studies By Use Of Portal-Vein Infusion In Rat .2. Influence Of Dose And Infusion Rate On Bioavailability Of Propranolol

Propranolol concentrations in the blood was determined after rapid femoral vein and 50 min portal vein infusion of several doses to rats. No propranolol appeared in the systemic circulation after intraportal infusion of doses less than approximately 2 mg/kg. The mean bioavailability of propranolol was 42% in a dose of 5 mg/kg and increased progressively with increasing dose. However, the area under the blood concentration-time curve after portal vein infusion of propranolol was found to vary with infusion rate. The hepatic elimination of the drug during the first pass through the liver after portal vein infusion was highly dose-dependent in lower doses, and highly rate-dependent in higher doses. Therefore, the bioavailability of the drug was dose and rate-dependent. However, in higher doses, it remained almost constant at a constant infusion rate.