TABLE 10

Ontogeny profile of hepatic CYP enzymes in Göttingen minipig based on metabolic activity, protein expression, and mRNA expression levels

Percentages represent expression/activity relative to adult levels.

Onset of Activity and/or ExpressionAdult Levels ReachedAge-Related Changes in Activity/ExpressionCommentsReferences
CYP1A2
 Catalytic activityM: −28 days (0.5%); F: −28 days (3%)M: NR (60% at 28 days); F: NR (81% at 28 days)Increased rapidlySingle study, not clear whether substrate is specific in Göttingen minipigs. Adult age: 822 days. Substrate: phenacetin O-deethylation. Methods: PLM. Strain: Göttingen minipig (M/F)Van Peer et al. (2017)
CYP2C9
 Catalytic activityM: −28 days (2%); F: −28 days (1.5%)M: NR (45% at 28 days); F: NR (28% at 28 days)Increased rapidlySingle study, not clear whether substrate is specific in Göttingen minipigs. Adult age: 822 days. Substrate: 4-hydroxylation of tolbutamide. Methods: PLM. Strain: Göttingen minipig (M/F)Van Peer et al. (2017)
CYP2D6
 Catalytic activityM: −28 days (0.4%); F: −28 days (1%)M: 28 days; F: NR (61% at 28 days)Increased rapidlySingle study, not clear whether substrate is specific in Göttingen minipigs. Adult age: 822 days. Substrate: dextromethorphan O-demethylation. Methods: PLM. Strain: Göttingen minipig (M/F)Van Peer et al. (2017)
CYP3A
 Catalytic activityM: −28 days (0.8%); F: −28 days (0.3%)M: NR (39% at 28 days); F: NR (41% at 28 days)Increased rapidlySingle study, not clear whether substrate is specific in Göttingen minipigs. Adult age: 822 days. Substrate: Luciferin-IPA, Midazolam. Methods: PLM. Strain: Göttingen minipig (M/F)Van Peer et al., (2014, 2015, 2017)
 Protein expressionM/F: −30 days (31%)150 days (85%)Increased rapidlySingle study, conflicting data between papers. Adult age: 822 days. Substrate: rabbit polyclonal anti-human anti-CYP3A4 antibody/CYP3A22, CYP3A29, CYP3A39, CYP3A46. Methods: PLM. Strain: Göttingen minipig (M/F)
  • F, female; IPA, isopropyl acetale; M, male; NR, not reported; PLM, pig liver microsome.