Presystemic elimination of drugs: theoretical considerations for quantifying the relative contribution of gut and liver.

From a consideration of the basic processes involved in drug elimination, the fraction of drug cleared by the gut and by the liver were described as functions of availability and hepatic clearance. For a drug given orally, a plot of the fraction of drug cleared by the gut or liver against alpha, a proportionality constant relating gut elimination following intravenous administration to that following oral administration, allowed an estimate of the possible contribution of gut and liver to presystemic elimination. This method was dependent only on the measurement of peripheral blood drug concentrations and urine levels. Application of the theory to published data for several drugs known to have a reduced availability after oral administration was used to illustrate the procedure.