“…CPA is a prodrug and requires bioactivation in the liver to 4-hydroxy-cyclophosphamide (4-OH-CPA), which is subsequently converted to the ultimate alkylating metabolite, phosphoramide mustard, and acrolein, a urotoxic metabolite (Ekhart et al, 2008). Various cytochrome P450 (CYP) enzymes have been implicated to catalyze the 4-hydroxylation of CPA to 4-OH-CPA including CYP2B6 (Xie et al, 2003), CYP2C9, and CYP3A4/5 (Roy et al, 1999), CYP2C19 (Griskevicius et al, 2003;Timm et al, 2005), and CYP2J2 (El-Serafi et al, 2015a). These enzymes are genetically polymorphic and may contribute to interindividual variation in CPA metabolic disposition and clinical response including chemotherapy-induced toxicities (Nakajima et al, 2007;Zanger et al, 2007;Ekhart et al, 2008).…”