Methotrexate, serum
Clinical Background:
Methotrexate (amethopterin) is an antimetabolite which by inhibiting dihydrofolate reductase (DHFR) depletes the intracellular pool of reduced folate. This in turn inhibits DNA synthesis.
It has a...
Methotrexate (amethopterin) is an antimetabolite which by inhibiting dihydrofolate reductase (DHFR) depletes the intracellular pool of reduced folate. This in turn inhibits DNA synthesis.
It has activity against a wide variety of tumours and both high and low dose regimes have been used in the treatment of conditions including leukaemia, choriocarcinoma and variety of solid tumours. At lower doses it appears to act as an immunosuppressant by acting selectively against lymphocytes. It has found use in the treatment of arthritis and psoriasis and as the possible only effective treatment for childhood inflammatory arthritis.
Because of its potent effect on embryogenesis, methotrexate is also used in the conservative treatment of ectopic pregnancy.
Methotrexate can be given orally, IV, IM or into the body cavity. Absorption following oral dosage is good but can be affected at high doses if given with antibiotics. It undergoes uptake, storage and metabolism in the liver where it is converted into polyglutamate forms that can persist for several months. The major elimination route is via the kidneys accounting for 80% body clearance. Clearance is biphasic with an initial half-life of 1.5 to 3.5 hours during the first 24hours. This is not dose related and is determined mainly by renal function. The prolonged half life 8 -15 hours may be increased by obstruction of the GI tract reducing biliary excretion.
Adverse effects of methotrexate are dose-related, organ dependent and a function of concentration and exposure duration. General cytotoxic side effects such as nausea, vomiting and hyperuricaemia occur along with the more specific problems of gastrointestinal mucositis, myelosuppression and hepatic and renal dysfunction.
The use of leucovorin “rescue” permits relatively safe administration of very high doses of methotrexate to achieve maximum antineoplastic activity. Since the degree of methotrexate cytotoxicity is related to the drugs concentration and to the duration of exposure, leucovorin rescue dosages must be high enough and last long enough to avoid methotrexate toxicity. Monitoring methotrexate concentrations and the rate of decline in serum during high dose therapy is essential when designing adequate leucovorin rescue dosages (see protocols).
Measurements are not required for low dose therapy unless overdose or toxicity is suspected or for assessment of compliance.
Test Details
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Discipline:
Biochemistry
Biochemistry
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Specimen Container Adult:
Serum (SST or plain tube)
Serum (SST or plain tube)
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Specimen Container Paediatric:
Serum (SST or plain tube)
Serum (SST or plain tube)
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Minimum Volume Adult:
1 mL blood
1 mL blood
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Minimum Volume Paediatric:
0.5 mL blood
0.5 mL blood
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Sample Stability:
Sample stability:
Before separation: unknown
After separation at +15° to +25°C: Unknown
at +2° to +8°C: 3 days
at -20°C: 6 monthsSample stability:
Before separation: unknown
After separation at +15° to +25°C: Unknown
at +2° to +8°C: 3 days
at -20°C: 6 months -
Interpretation:
Protocol: EUROLAB-LB-02
Diagnosis: T Cell Lymphoma
Time from start of MTX Infusion (h) MTX level expected (umol/L)
T + 24 < 150
T + 36 < 3
T + 42 < 1
T + 48 < 0.4
T + 54 < 0.25
Protocol: EUROAMO...Read MoreProtocol: EUROLAB-LB-02
Diagnosis: T Cell Lymphoma
Time from start of MTX Infusion (h) MTX level expected (umol/L)
T + 24 < 150
T + 36 < 3
T + 42 < 1
T + 48 < 0.4
T + 54 < 0.25
Protocol: EUROAMOS-1
Diagnosis: Osteosarcoma
Time from start of MTX Infusion (h) MTX level expected (umol/L)
T + 24 < 20
T + 48 < 2
T + 72 < 0.2
T + 96 < 0.2
Aminopterin (antineoplastic agent) and APA (a minor methotrexate metabolite) cross react significantly. No other structurally related compounds interfere.
No significant interference in haemolysed, lipaemic or icteric samples. -
Other Info:
Lithium heparin, EDTA and fluoride oxalate plasma samples also acceptable
Lithium heparin, EDTA and fluoride oxalate plasma samples also acceptable
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Routine Contact Name:
Duty Biochemist
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Routine Telephone:
Freeman: 0191 244 8889
RVI: 0191 282 9719Freeman: 0191 244 8889
RVI: 0191 282 9719 -
Routine Email: