Flavin-containing monooxygenase 3 (FMO3) role in busulphan metabolic pathway
Fig 3
The effect of FMO3 inhibition on concentration-time curve of busulphan (Bu) and tetrahydrothiophene (THT) in mice.
To study the effect of FMO3 inhibition on Bu kinetics, animals were divided into three groups. All experiments were run with 3 mice per time point in each group. Animals were euthanized and blood samples collected at different time points. Group1. A single dose of Bu (25mg/kg) was administered i.p. to mice Group2. A single dose of Bu (25mg/kg) was administered i.p. 24h after pretreatment with the FMO3-inhibitor phenylthiourea (PTU, 3mg/kg; i.p.) for 3 days. Group3. Bu (25mg/kg) was administered concomitantly with a high dose of THT (17.6mg/kg). A. Pretreatment with PTU significantly (P<0.05) increased plasma levels of Bu (Δ, dashed line) compared to that observed when Bu was administered alone (□, dotted line). THT, when given together with Bu, also affected Bu metabolism and increased in Bu plasma concentrations (○; solid line) compared to Bu alone. B. Pretreatment with PTU significantly (P<0.05) increased plasma concentrations of Bu first stable metabolite (THT) in mice injected with Bu (Δ, dashed line) compared to that observed when Bu was administered alone (□, dotted line). THT concentrations in mice injected with Bu and PTU (Δ, dashed line) were almost the same as in mice injected with Bu and concomitant high doses of THT without pretreatment with PTU (○; solid line).