TOX 300 Lecture 4: Biotransformation
Document Summary
Oral bioavailability = the fraction of an orally administered xenobiotic that reaches the systemic circulation in an unchanged form. Aucoral = area under the curve; integrates the plasma concentration of a drug over time. Auciv = intravenous administration is 100% bioavailable to the body as it directly enters the systemic circulation. The epithelial cell lining the intestines have some capacity of biotransformation. Phase 1 tries to make the xenobiotic more water-soluble but usually it is not enough. *remember the enzyme and the cofactor, and be able to recognize the (cid:272)ofa(cid:272)tor"s general stru(cid:272)ture. Glutathione conjugates are rearranged to mercapturic acid and commonly excreted in bile (cid:862)happy fa(cid:272)e pathway(cid:863) (cid:862)sad fa(cid:272)e pathway(cid:863) napthalene epoxide covalent binding to dna, protein. Acetaminophen already has an oh group so it doesn"t need to undergo phase 1 rea(cid:272)tion. Happy face pathway: acetaminophen udp-gt/udp-ga acetaminophen glucuronide, acetaminophen sulfotansferase/paps acetaminophen sulfate, napqi detoxified by gsh glutathione conjugate.
