Flavin-containing monooxygenase 3 (FMO3) role in busulphan metabolic pathway
Fig 6
The effect of voriconazole treatment on busulphan and tetrahydrothiophene kinetics in patients conditioned prior to HSCT.
Busulphan (Bu) and tetrahydrothiophene (THT) were determined in two patients undergoing stem cell transplantation and conditioned with high doses of busulphan (2mg/kg b.i.d.) for four days. One patient received only Bu during conditioning, while the other patient was concomitantly administered voriconazole for Candida infection (3mg/kg i.v. b.i.d). Samples were collected at several time points for therapeutic drug monitoring. (A) Significantly (P<0.05) higher levels of Bu were observed in the patient receiving concomitant voriconazole (Δ, dashed line), compared to the levels observed after the same dose of Bu when administered alone (□, solid line). (B) THT levels were significantly (P<0.05) higher already after the first Bu dose with high accumulation and slower metabolism (Δ, dashed line) compared to Bu alone (□, solid line). Voriconazole was withdrawn after Bu second dose and Bu dose was reduced to 1.2mg/kg b.i.d for two days.