Pharmacokinetics of drugs subject to enterohepatic circulation.

The influence of the changes in biliary excretion and reabsorption rates on the pharmacokinetics of drugs subject to enterohepatic circulation was examined analytically. A recently proposed two-compartment model with drug elimination occurring in each compartment was adapted to represent the body and the GI tract. Enhanced reabsorption was equivalent to biliary excretion rate reduction, except that the latter always decreased alpha and prolonged the alpha-phase half-life while the former always increased alpha and shortened the half-life. However, depending on the relative values of the two elimination rate constants, biliary excretion reduction (or reabsorption enhancement) could either increase or decrease the terminal drug half-life (beta-phase). Whether the terminal drug half-life was prolonged or shortened, a biliary excretion reduction always increased the area under the plasma decay curve for intravenous and oral doses and also raised the steady-state drug level in the body for constant-rate intravenous infusion. As a consequence, the lethality, toxicity, or effectiveness of the drug will be increased for patients with impaired bile flow or enhanced drug reabsorption; therefore, the clinical dosage may have to be reduced.