Drug Dosing Issues and Resources

As with renal impairment, the threshold at which an adjustment of dosage may be necessary depends not only on the route of elimination, but the mechanisms involved. These dosage precautions are essential. Drug classifications rarely point out differences between members regarding the pathways of metabolism. Hepatic metabolism is complex, but it can generally be broadly grouped into two broad types of reactions/pathways: Phase I and Phase II reactions.

Phase I reactions include reactions which greatly modify the chemical structure of the drug. In a way, these are more difficult reactions to perform. The ability of the liver to carry out these functions can be significantly decreased at moderate levels of functional impairment. Phase II reactions are in many ways “simpler” from a chemical standpoint, and the ability to perform them can be preserved even in significant hepatic damage. For this reason, it is important to know not only whether a drug is metabolized, but also the type of metabolism. In this way a therapeutic dosage may be determined.