A convenient method for estimating the quantity of drug eliminated by the routes other than hepatic metabolism and renal excretion and the fraction of drug that reaches the "first pass" after oral administration.
The comparison of routine pharmacokinetic data obtained after intravenous and oral drug administration allows to figure out that some quantity of drug, which reached the systemic circulation, was eliminated from the body by routes other than hepatic metabolism and renal excretion. This quantity is equal or exceeds the certain minimum value, which can be calculated from a simple equation obtained in the article. If the minimum value is equal to zero, then the maximum possible fraction of orally administered drug, that is, absorbed into the gut wall and gets through it unchanged, can be calculated. The examples considered indicate that the quantity of drug eliminated not by liver metabolism or kidney excretion could be quite substantial (exceeds half of the dose that reached the circulation).
Berezhkovskiy
Leonid M
LM
Roche Palo Alto LLC, Palo Alto, California 94304, USA. leo.berezhkovskiy@roche.com
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D000882:Haplorhini; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D010599:Pharmacokinetics; D051381:Rats
D004364:Pharmaceutical Preparations