TABLE 12

Ontogeny profile of hepatic CYP enzymes and hepatic CYP content in Beagle dog based on metabolic activity and protein expression levels

Percentages represent expression/activity relative to adult levels.

Onset of Activity and/or ExpressionAdult Levels ReachedAge-Related Changes in Activity/ExpressionCommentsReferences
CYP1A1
 Catalytic activity7 days (59%)21 daysNo changesSingle study, not clear whether substrate is specific in Beagle dogs. Fetal development: NR. Adult age: 1050 days. Substrate: p-nitroanisole O-demethylation. Methods: DLM. Strain: Beagle dog (M)Tanaka et al. (1998)
CYP1A2
 Catalytic activity7 days (58%)105 daysIncreased rapidly/no changesSingle study, not clear whether substrate is specific in Beagle dogs. Fetal development: NR. Adult age: 1050 days. Substrate: caffeine N-demethylation. Methods: DLM. Strain: Beagle dog (M)Tanaka et al. (1998)
CYP2C9
 Catalytic activity7 days (94%)7 daysIncreased rapidly/inconsistent patternSingle study, not clear whether substrate is specific in Beagle dogs. Fetal development: NR. Adult age: 1050 days. Substrate: phenytoin hydroxylation. Methods: DLM. Strain: Beagle dog (M)Tanaka et al. (1998)
CYP2E1
 Catalytic activity7 days (66%)21 daysIncreased rapidly/no changesSingle study, not clear whether substrate is specific in Beagle dogs. Fetal development: NR. Adult age: 1050 days. Substrate: aniline hydroxylation. Methods: DLM. Strain: Beagle dog (M)Tanaka et al. (1998)
CYP3A4/5
 Catalytic activity7 days (77%)NR (variable)Inconsistent patternSingle study, not clear whether substrate is specific in Beagle dogs. Fetal development: NR. Adult age: 1050 days. Substrate: erythromycin N-demethylation. Methods: DLM. Strain: Beagle dog (M)Tanaka et al. (1998)
CYP3A/2B
 Catalytic activity7 days (65%)49 daysIncreased rapidly/no changesSingle study, not clear whether substrate is specific in Beagle dogs. Fetal development: NR. Adult age: 1050 days. Substrate: benzphetamine N-demethylation. Methods: DLM. Strain: Beagle dog (M)Tanaka et al. (1998)
CYP2C/2E1/3A
 Catalytic activity7 days (50%)NR (154% at 21 days)Increased rapidly/inconsistent patternSingle study, not clear whether substrate is specific in Beagle dogs. Fetal development: NR. Adult age: 1050 days. Substrate: trimethadion N-demethylation. Methods: DLM. Strain: Beagle dog (M)Tanaka et al. (1998)
Cytochrome P450 content
 Protein expressionNRNRInconsistent patternSingle study. Fetal development: NR. Adult age: 1050 days. Methods: Omura and Sato (DLM). Unit: nanomoles per milligram microsomal proteinTanaka et al. (1998)
  • DLM, dog liver microsome; M, male; NR, not reported.