Barnes-Seeman, D. et al. ACS Med. Chem. Lett., 2013, 4 (6), pp 514–516
Novartis Institutes for Biomedical Research
“This review examines the abundance of metabolites relative to the total parent drug [metabolite-to-parent (M/P) ratio] from 125 drugs in relation to their structural and physicochemical characteristics, lipoidal permeability, protein binding, and fractional formation from parent (fm). Our analysis suggests that fm is the major determinant of total drug M/P ratio for amine, alcohol, N- and S-oxide, and carboxylic acid metabolites.”
Two common patterns associated with Detoxication:
Detoxification is the process of removing toxins from the body, while detoxication is the process of preventing toxic entities from entering the body in the first place.
Examples of detoxification are: Administration of chelators for heavy metal poisoning, hyperbaric oxygen treatment for carbon monoxide poisoning and treatment of ethylene glycol poisoning with ethanol.
Stiborova M., Frei E., Arlt V.M., Schmeiser H.H.
Enzymes may be involved in the bioactivation of AA include NAD(P)H:quinone oxidoreductase (NQO1), followed by cytochrome P450 (CYP) 1A1/2 in hepatic microsomes, and NADPH:CYP reductase (NPR) in renal microsomes. In addition, prostaglandin H synthase (cyclooxygenase, COX) highly expressed in urothelial tissue is also able to bioactivate AAI.
The oxidation of AAI to aristolochic acid Ia (AAIa) and conjugation reactions to form N– and O-glucuronide, the O-acetate and the O-sulfate esters have been suggested to be detoxification pathways.
Aristolochic acids are carcinogenic, mutagenic, and nephrotoxic compounds that cause Balkan endemic nephropathy and “Chinese herbs nephropathy”.