Phenotypes Associated with This Genotype

Genotype
MGI:3775628

• Allelic Composition: Cyp3a13^tm1Nki/Cyp3a13^tm1Nki; Del(5Cyp3a57-Cyp3a59)2Nki/Del(5Cyp3a57-Cyp3a59)2Nki; Tg(APOE-CYP3A4)A1Nki/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

homeostasis/metabolism

abnormal xenobiotic pharmacokinetics ( J:127366 )

• docetaxel M-2 metabolites are not detected in intestinal microsomes unlike in wild-type microsomes treated with docetaxel

• plasma docetaxel are higher than in wild-type mice following intravenous administration

• oral administration of docetaxel results in a 2.2-fold reduction of plasma levels compared to in Del(15Cyp3a57-Cyp3a59)1Ahs Cyp3a13^tm1Ahs homozygotes

• however, M-2 metabolites are detected in hepatic microsomes

• docetaxel accumulation in the liver is decreased 19-fold compared to in Del(15Cyp3a57-Cyp3a59)1Ahs Cyp3a13^tm1Ahs homozygotes

• however, plasma docetaxel levels following intravenous injection are decreased 5.5-fold compared to in Del(15Cyp3a57-Cyp3a59)1Ahs Cyp3a13^tm1Ahs homozygotes to near normal levels and mice exhibit near normal clearance of docetaxel

• oral bioavailability is increased to 21% compared to 8.1% in wild-type mice