UGT1A4
From PubPK
UGT1A4 metabolizes the antidepressants amitriptyline and imipramine, the antipsychotic clozapine, quinine antimalarials, and tamoxifen (Radominska-Pandya et al., 1999; Ogura et al., 2006; Uchaipichat et al., 2006).
The development of UGT1A4 activity in pediatric livers was investigated by Miyagi and Collier (2007). When a constant rate of enzyme development was assumed, maximum activity of UGT1A4 occurs at 1.4 years of age. When the intrinsic hepatic clearance of trifluoperazine was scaled with an allometric model, hepatic clearance of trifluoperazine by UGT1A4 did not reach maximum levels until 18.9 years of age.
References
- Miyagi SJ and Collier AC (2007) Pediatric development of glucuronidation: The ontogeny of hepatic UGT1A4 Drug Metab Dispos 35:1587-1592.
- Ogura K, Ishikawa Y, Kaku T, Nishiyama T, Ohnuma T, Muro K, and Hiratsuka A (2006) Quaternary ammonium-linked glucuronidation of trans-4-hydroxytamoxifen, an active metabolite of tamoxifen, by human liver microsomes and UDP-glucuronosyltransferase 1A4 Biochem Pharmacol 71:1358–1369.
- Radominska-Pandya A, Czernik P, Little J, Battaglia E, and Mackenzie P (1999) Structural and functional studies of UDP-glucuronosyl transferases Drug Metab Rev 31:817–899.
- Uchaipichat V, Mackenzie P, Elliot D, and Miners J (2006) Selectivity of substrate (trifluoperazine) and inhibitor (amitriptyline, androsterone, canrenoic acid, hecogenin, phenylbutazone, quinidine, quinine, and sulfinpyrazone) “probes” for human UDP-Glucuronosyltransferases Drug Metab Dispos 34:449–456.
