title: Methotrexate and 7-hydroxy-methotrexate pharmacokinetics following intravenous bolus administration and high-dose infusion of methotrexate.
abstract: The pharmacokinetics of methotrexate and 7-hydroxy-methotrexate were studied in patients undergoing very high-dose methotrexate monotherapy. The patients received, first, two methotrexate intravenous bolus test doses (50 mg/m2) one with and one without concomitant administration of folinic acid (15 mg every 6 h) in a random sequence, and, second, an 8 h infusion, individualized to achieve a peak plasma concentration of 5 X 10(-4) M methotrexate (infusion rates greater than 1000 mg/h). Methotrexate and 7-hydroxy-methotrexate concentrations were measured by specific radioimmunoassays and the data were analysed simultaneously by an integrated pharmacokinetic model. Following test dose administration, methotrexate and 7-hydroxy-methotrexate plasma concentration kinetics were best described by assuming that methotrexate elimination (and 7-hydroxy-methotrexate formation) occurred from a peripheral compartment reaching rapid equilibrium with the plasma. Folinic acid administration did not influence the disposition of either compound. Following the infusion, a significant (P less than 0.01) decrease of methotrexate total plasmatic clearance occurred without modification of 7-hydroxy-methotrexate formation and elimination.
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D008954:Models, Biological; D013997:Time Factors
chemical_list: D002955:Leucovorin; C011864:7-hydroxymethotrexate; D008727:Methotrexate