Also, UGT1A1 conjugates bilirubin and bilirubin glucuronidation is another risk factor for increased toxicity

De-conjugation by β-glucuronidases
The intestinal bacteria produced β-glucuronidases that de-conjugate SN-38G to SN-38 resulting in entero-hepatic re-circulation of SN-38. Metabolism by cytochrome P450 enzymes
Irinotecan is metabolized by intrahepatic cytochrome P450 enzymes, CYP3A4 and CYP3A5 into inactive metabolites APC (7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin) and NPC (7-ethyl-10-[4-amino-1-piperidino] carbonyloxycamptothecin). NPC can be further converted by CES1 and CES2 in the liver to SN-38. Induction or inhibition of CYP3A enzymes by smoking, some herbs and medications may result in interactions with irinotecan. Transport to bile
Irinotecan is transported to bile by the ATP-binding cassette (ABC) transporter proteins: ABCB1, ABCC1, ABCC2, and ABCG2. Elimination
Irinotecan clearance is mainly biliary (66%) and estimated 12–21 L/h/m2. All metabolites, except SN-38G, are mainly excreted in feces. Irinotecan  elimination half-lives were reported between 5 to18 h. SN-38 half-lives were reported between  6 and 32 h.There is high (30%) interindividual variability in irinotecan pharmacokinetic parameters which can be altered by several factors including age, sex, dose, administration timing, hepatic function, enzyme activity or hematocrit levels. Pharmacogenomics
Irinotecan is converted by an enzyme into its active metabolite SN-38, which is in turn inactivated by the enzyme UGT1A1 by glucuronidation. *28 variant patients
People with variants of the UGT1A1 called TA7, also known as the "*28 variant", express fewer UGT1A1 enzymes in their liver and often have Gilberts syndrome. During chemotherapy, they effectively receive a larger than expected dose because their bodies are not able to clear irinotecan as fast as others.
Furthermore, it has been demonstrated that individuals with otitis media have more depression/anxiety-related disorders compared to individuals with normal hearing. Once the infections resolve and hearing thresholds return to normal, childhood otitis media may still cause minor and irreversible damage to the middle ear and cochlea. More research on the importance of screening all children under 4 years old for otitis media with effusion needs to be performed. Epidemiology
Acute otitis media is very common in childhood. It is the most common condition for which medical care is provided in children under five years of age in the US. Acute otitis media affects 11% of people each year (709 million cases) with half occurring in those below five years. Chronic suppurative otitis media affects about 5% or 31 million of these cases with 22.6% of cases occurring annually under the age of five years. Otitis media resulted in 2,400 deaths in 2013—down from 4,900 deaths in 1990. Etymology
The term otitis media is composed of otitis, Ancient Greek for "inflammation of the ear", and media, Latin for "middle". References
External links
Neff MJ (June 2004). "AAP, AAFP, AAO-HNS release guideline on diagnosis and management of otitis media with effusion". American Family Physician. 69 (12): 2929–31. PMID 15222658.