Population pharmacokinetics of methotrexate in the guinea pig

The population pharmacokinetics of an antitumoral and antiinflammatory agen t, methotrexate (MTX), a folic acid antagonist, was studied in guinea pigs. Animals received an acute intraperitoneal injection of 0.25, 1 or 5 mg/kg MTX, Blood sampling was carried out for 12 hrs, after MTX administration an d plasma drug concentrations were measured by fluorescence polarization imm unoassay, The pharmacokinetic (PK) parameters were computed using the bayes ian population model. MTX reached the level of detection at ? hrs, for the animals injected with the lowest dose (0.25 mg/kg), at 3.5 hrs. for those a nimals which had the intermediate dose (1 mg/kg) and more than 6 hrs, for a nimals having received the highest dose (5 mg/kg), Each kinetic parameter ( half life, total clearance - CLt, volume of distribution at steady state - VDSS, mean residence time - MRT - and area under curve - AUC) didn't show a ny significant difference between doses. MTX kinetic was linear for the fir st two doses (0.25 and 1 mg/kg MTX) and non-linear thereafter. MTX presente d a one compartment distribution.