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EC number: 212-084-8 | CAS number: 760-93-0
Non-compartmental analysis of the blood concentration data for MAA at the two doses, gives volumes of distribution of 23 ml (10 mg kg-1) and 35 ml (20 mg kg-1). The clearance of MAA was calculated to be 0.324 L hr-1 SRW-1 at the 10 mg kg-1 dose and 0.25 L hr-1 SRW-1 at the 20 mg kg-1 dose. The change in clearance from the lower dose to the higher dose indicates non-linear saturable metabolism in the rat.
Based on that information, the following kinetic parameters were determined from a simultaneous fit of the in vivo data to a one-compartment model with non-linear elimination (Vss = 0.039 L/SRW; Vmax = 19.8 mg/hrxSRW; Km = 20.3 mg/L; SRW: standard rat weight = 250 g) the half-life of MAA in blood was calculated to 1.7 min.
The PBPK model data were validated by i.v. administration of MAA in rats and subsequent analysis of blood from the tail vein.
In conclusion, from a simultaneous fit of the in vivo data to a one-compartment model with non-linear elimination, the half-life of MAA in blood was calculated to 1.7 min.
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