UDP-glucuronosyltransferase 1A4-mediated N2-glucuronidation is the major metabolic pathway of lamotrigine in chimeric NOG-TKm30 mice with humanised-livers

References

• Argikar UA, Remmel RP. 2009. Variation in glucuronidation of lamotrigine in human liver microsomes. Xenobiotica. 39(5):355–363.
   PubMed Web of Science ®Google Scholar
• Bateman TJ, Reddy VG, Kakuni M, Morikawa Y, Kumar S. 2014. Application of chimeric mice with humanized liver for study of human-specific drug metabolism. Drug Metab Dispos. 42(6):1055–1065.
   PubMed Web of Science ®Google Scholar
• Bock KW. 2003. Vertebrate UDP-glucuronosyltransferases: functional and evolutionary aspects. Biochem Pharmacol. 66(5):691–696.
   PubMed Web of Science ®Google Scholar
• Chen H, Grover S, Yu L, Walker G, Mutlib A. 2010. Bioactivation of lamotrigine in vivo in rat and in vitro in human liver microsomes, hepatocytes, and epidermal keratinocytes: characterization of thioether conjugates by liquid chromatography/mass spectrometry and high field nuclear magnetic resonance spectroscopy. Chem Res Toxicol. 23(1):159–170.
   PubMed Web of Science ®Google Scholar
• Chiu SH, Huskey SW. 1998. Species differences in N-glucuronidation. Drug Metab Dispos. 26(9):838–847.
   PubMed Web of Science ®Google Scholar
• Doig MV, Clare RA. 1991. Use of thermospray liquid chromatography-mass spectrometry to aid in the identification of urinary metabolites of a novel antiepileptic drug, Lamotrigine. J Chromatogr. 554(1–2):181–189.
   PubMed Web of Science ®Google Scholar
• Foti RS, Dalvie DK. 2016. Cytochrome P450 and non-cytochrome P450 oxidative metabolism: contributions to the pharmacokinetics, safety, and efficacy of xenobiotics. Drug Metab Dispos. 44(8):1229–1245.
   PubMed Web of Science ®Google Scholar
• Fujiwara R, Yoda E, Tukey RH. 2018. Species differences in drug glucuronidation: humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans. Drug Metab Pharmacokinet. 33(1):9–16.
   PubMed Web of Science ®Google Scholar
• Hasegawa M, Kawai K, Mitsui T, Taniguchi K, Monnai M, Wakui M, Ito M, Suematsu M, Peltz G, Nakamura M, et al. 2011. The reconstituted 'humanized liver' in TK-NOG mice is mature and functional. Biochem Biophys Res Commun. 405(3):405–410.
   PubMed Web of Science ®Google Scholar
• Hawes EM. 1998. N+-glucuronidation, a common pathway in human metabolism of drugs with a tertiary amine group. Drug Metab Dispos. 26(9):830–837.
   PubMed Web of Science ®Google Scholar
• Kamimura H, Ito S, Chijiwa H, Okuzono T, Ishiguro T, Yamamoto Y, Nishinoaki S, Ninomiya SI, Mitsui M, Kalgutkar AS, et al. 2017. Simulation of human plasma concentration-time profiles of the partial glucokinase activator PF-04937319 and its disproportionate N-demethylated metabolite using humanized chimeric mice and semi-physiological pharmacokinetic modeling. Xenobiotica. 47(5):382–393.
   PubMed Web of Science ®Google Scholar
• Luffer-Atlas D, Atrakchi A. 2017. A decade of drug metabolite safety testing: industry and regulatory shared learning. Expert Opin Drug Metab Toxicol. 13(9):897–900.
   PubMed Web of Science ®Google Scholar
• Magdalou J, Herber R, Bidault R, Siest G. 1992. In vitro N-glucuronidation of a novel antiepileptic drug, lamotrigine, by human liver microsomes. J Pharmacol Exp Ther. 260(3):1166–1173.
   PubMed Web of Science ®Google Scholar
• Maggs JL, Naisbitt DJ, Tettey JN, Pirmohamed M, Park BK. 2000. Metabolism of lamotrigine to a reactive arene oxide intermediate. Chem Res Toxicol. 13(11):1075–1081.
   PubMed Web of Science ®Google Scholar
• Martignoni M, Groothuis GM, de Kanter R. 2006. Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opin Drug Metab Toxicol. 2(6):875–894.
   PubMed Web of Science ®Google Scholar
• Schaefer WH. 2006. Reaction of primary and secondary amines to form carbamic acid glucuronides. Curr Drug Metab. 7(8):873–881.
   PubMed Web of Science ®Google Scholar
• Troberg J, Jarvinen E, Muniz M, Sneitz N, Mosorin J, Hagstrom M, Finel M. 2015. Dog UDP-glucuronosyltransferase enzymes of subfamily 1A: cloning, expression, and activity. Drug Metab Dispos. 43(1):107–118.
   PubMed Web of Science ®Google Scholar
• Uehara S, Higuchi Y, Yoneda N, Kawai K, Yamamamoto M, Kamimura H, Iida Y, Oshimura M, Kazuki Y, Yamazaki H, et al. in press. An improved TK-NOG mouse as a novel platform for humanized liver that overcomes limitations in both male and female animals. Drug Metab Pharmacokinet.
   Web of Science ®Google Scholar
• Uehara S, Higuchi Y, Yoneda N, Yamazaki H, Suemizu H. 2019. Expression and inducibility of cytochrome P450s in human hepatocytes isolated from chimeric mice with humanised livers. Xenobiotica. 49(6):678–687.
   PubMed Web of Science ®Google Scholar
• Uehara S, Yoneda N, Higuchi Y, Yamazaki H, Suemizu H. 2020a. Human aldehyde oxidase 1-mediated carbazeran oxidation in chimeric TK-NOG mice transplanted with human hepatocytes. Drug Metab Dispos. 48(7):580–586.
   PubMed Web of Science ®Google Scholar
• Uehara S, Yoneda N, Higuchi Y, Yamazaki H, Suemizu H. 2020b. Metabolism of desloratadine by chimeric TK-NOG mice transplanted with human hepatocytes. Xenobiotica. 50(6):733–740.
   PubMed Web of Science ®Google Scholar
• Uehara S, Yoneda N, Higuchi Y, Yamazaki H, Suemizu H. 2021. Methyl-hydroxylation and subsequent oxidation to produce carboxylic acid is the major metabolic pathway of tolbutamide in chimeric TK-NOG mice transplanted with human hepatocytes. Xenobiotica. 51(5):582–589.
   PubMed Web of Science ®Google Scholar
• Uno Y, Takahira R, Murayama N, Ishii Y, Ikenaka Y, Ishizuka M, Yamazaki H, Ikushiro S. 2018. Molecular and functional characterization of UDP-glucuronosyltransferase 1A in cynomolgus macaques. Biochem Pharmacol. 155:172–181.
   PubMed Web of Science ®Google Scholar
• Guidance for industry: safety testing of drug metabolites. 2016. US Food and Drug Administration; [accessed 2021 July 23] https://www.fda.gov/regulatory-information/search-fda-guidance-documents/safety-testing-drug-metabolites/.
   Google Scholar
• Van Vleet TR, Liu H, Lee A, Blomme EAG. 2017. Acyl glucuronide metabolites: implications for drug safety assessment. Toxicol Lett. 272:1–7.
   PubMed Web of Science ®Google Scholar