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Methotrexate test-dose protocol in the presence of 7-hydroxy-methotrexate
- Source :
- European Journal of Cancer and Clinical Oncology. 23:481-485
- Publication Year :
- 1987
- Publisher :
- Elsevier BV, 1987.
-
Abstract
- Methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX) plasma concentration-time curves (AUC) have been analyzed in 24 patients after different routes of MTX administration. After an i.v. bolus (50 mg/m2), the AUC for 7-OH-MTX is correlated with that for MTX and inversely correlated with the MTX plasma clearance. When MTX is administered with plasma steady level standardization, using the test-dose protocol, at a level of 10(-5) M over 36 hr (10(-5), 36 hr), 7-OH-MTX-AUC is still correlated with the i.v. bolus pharmacokinetic parameters. The dose prediction using the classical test-dose protocol provides a less efficient MTX dose adjustment at 5 X 10(-4) M over 8 hr (5.10(-4), 8 hr) and the hydroxylation process is no more correlated with the i.v. parameters. On the opposite, upon 6 successive infusions with 10(-5), 36 hr or 5.10(-4), 8 hr protocols, the plasma concentrations of 7-OH-MTX are not significantly modified. This suggests that the hydroxylation process is not inducible.
- Subjects :
- Adult
musculoskeletal diseases
medicine.medical_specialty
Test dose
Adolescent
medicine.drug_class
Metabolite
Hydroxylation
Antimetabolite
chemistry.chemical_compound
Bolus (medicine)
Pharmacokinetics
immune system diseases
Internal medicine
Blood plasma
medicine
Humans
heterocyclic compounds
Child
Infusions, Intravenous
skin and connective tissue diseases
Aged
Osteosarcoma
Middle Aged
Methotrexate
Endocrinology
Oncology
chemistry
Head and Neck Neoplasms
Injections, Intravenous
medicine.drug
Subjects
Details
- ISSN :
- 02775379
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- European Journal of Cancer and Clinical Oncology
- Accession number :
- edsair.doi.dedup.....2c36f090ee761e25df99a99cc31976a2