Pharmacokinetics of methotrexate and 7-hydroxy-methotrexate after high-dose (33.6 g/m2) methotrexate therapy.
We have measured MTX and 7-OH-MTX in plasma and urine samples from a 9-year-old boy treated with six consecutive 24-h IV high-dose MTX courses (33.6 g/m2) after a relapse of ALL. The between-course pharmacokinetics of MTX and 7-OH-MTX were found to be highly reproducible. Both MTX and 7-OH-MTX elimination followed a biphasic curve, initial half-lives (t1/2(alpha] being 2.86 +/- 0.44 h and 5.14 +/- 0.46 h (mean +/- SD) and second-phase biological half-lives (t1/2(beta] being approximately 18 and 16 h, respectively. The apparent volume of distribution for MTX was 0.8 L/kg, whereas the corresponding value for 7-OH-MTX was threefold less. Since clearance of MTX was within the range reported for lower doses, the data suggest that MTX pharmacokinetics are not dose-dependent up to 33.6 g/m2.
Slørdal
L
L
Department of Pharmacology, Institute of Medical Biology, University of Tromsø, Norway.
Kolmannskog
S
S
Prytz
P S
PS
Moe
P J
PJ
Aarbakke
J
J
D002648:Child; D003131:Combined Modality Therapy; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008727:Methotrexate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000601:surgery
C011864:7-hydroxymethotrexate; D008727:Methotrexate