Methotrexate and 7-hydroxy-methotrexate pharmacokinetics following intravenous bolus administration and high-dose infusion of methotrexate

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/m 2 ) one with and one without concomitant administration of folinic acid (1...

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Veröffentlicht in:European journal of cancer & clinical oncology 1987-09, Vol.23 (9), p.1385-1390
Hauptverfasser: Bore, Patrick, Bruno, Rene, Lena, Nicole, Favre, Roger, Cano, Jean Paul
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Sprache:eng
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Zusammenfassung: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/m 2 ) 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 × 10 −4 M methotrexate (infusion rates > 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 methotexate 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 < 0.01) decrease of methotrexate total plasmatic clearance occurred without modification of 7-hydroxy-methotrexate formation and elimination.
ISSN:0277-5379
DOI:10.1016/0277-5379(87)90124-6