Pharmacokinetics of reduced folates after short-term infusion of d, 1-folinic acid.

After the use of d,1-folinic acid (d,1-CHO-THF), pharmacokinetic measurements should take into account 1-CHO-THF and its metabolite 1-methyltetrahydrofolic acid (1-CH3-THF) as well as d-CHO-THF. For this purpose, we developed a simple and rapid assay by combining reversed-phase HPLC to determine total levels of d,1-CHO-THF and CH3-THF and chiral HPLC to separate the biologically active 1-CHO-THF from the inactive d-CHO-THF. We investigated the pharmacokinetics after short-term infusion of 300 mg d,1-CHO-THF in ten healthy volunteers.

Pharmacokinetics of methotrexate during regional hyperthermia in a pig model.

In the pig model, regional hyperthermia in the gluteus was combined with the infusion of 150 mg MTX over a period of 100-120 min. The pharmacokinetic data reveal that this approach is capable of simulating the situation that is necessary and achievable in medium-dose MTX therapy of human tumours. Under MTX infusion, serum levels in the region of 10(-5) M are attained.

Methotrexate and methotrexate polyglutamates in human sarcoma metastases after high-dose methotrexate therapy.

The methotrexate concentrations in the lungs or cutaneous metastases of patients with osteogenic or soft-tissue sarcoma were determined at different times after a high-dose methotrexate therapy. The levels in the metastases were 0.964 to 2.

Pharmacokinetics of erythrocyte methotrexate after high-dose methotrexate.

Erythrocyte methotrexate (MTX) concentrations were determined in 10 patients with metastatic osteogenic or soft tissue sarcoma after 52 cycles of high-dose methotrexate (HDMTX). In contrast to serum MTX, pharmacokinetics of erythrocyte MTX showed three distinct phases: A rapid decrease to a nadir 2-3 days after MTX was followed by a significant rise of erythrocyte MTX until days 10-14. Subsequently there was a third phase, with a definite decrease of erythrocyte MTX concentrations with half-lives of 30-40 days.

Ferrokinetics after high-dose methotrexate therapy.

After high-dose methotrexate with doses ranging from 2-10 g/m2, ferrokinetics were performed in 11 patients with different tumors. Iron-III-citrate-59Fe was injected at methotrexate serum concentrations ranging between 2.7 x 10(-7) -1.