homeostasis/metabolism
• 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 Cyp3a13tm1Ahs 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 Cyp3a13tm1Ahs homozygotes
• however, plasma docetaxel levels following intravenous injection are decreased 5.5-fold compared to in Del(15Cyp3a57-Cyp3a59)1Ahs Cyp3a13tm1Ahs 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
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