Biomedical subjects
Publications and source records attributed to L Skibińska.
The average values of Vm and Michelis constant Km were determined for enzyme isolated from liver (12.23 mumole/min and 3.2 x 10(-6) mole/dm3. respectively). The enzyme was stable over four months at -20 degrees C. Dissociation constant enzyme-inhibitor (methotrexate) complex Ki is 3.7 x 10(-8) mole/dm3. The reaction rate was sensitive to temperature (5 degrees C increase doubled maximum reaction rate).
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Pharmacokinetics of methotrexate renal elimination was investigated in patients with cancer given a single intravenous injection. Elimination coefficient ke (0.151 + 0.05 h-1) and half-life t0.5 (5.3 +/- 2.9 h) were calculated. A percentage of methotrexate dose eliminated with the urine was determined (26.0-97.1%) in both unchanged and bound forms. It was found that methotrexate is eliminated in the form of glucuronates and sulfates (2-25% of the administered dose). It was also noted, that pH of the urine exerts an effect on the amount of eliminated methotrexate.
The percentage of methotrexate (MTX) binding to plasma protein was 50.4 +/- 1.9 in healthy subject, and 32.3 +/- 3.6 in patients with cancer (breast carcinoma in most cases). Drugs used in combination with MTX in therapy (vincristine, vinblastine, cyclophosphamide, 5-fluorouracil, prednisone) depress the MTX binding to albumins. MTX binds to two kinds of albumins binding sites, with different binding constants: K1 = 8.88 mM-1 and K2 = 1.76 mM-1.
Pharmacokinetics of the intrathecally given methotrexate (MTX) for protection of the central nervous system was studied in 17 children with acute lymphoblastic leukemia (ALL). MTX plasma levels were assayed by enzymatic inhibition. The first order rate constants for the absorption, distribution and elimination phases were calculated on the base of an open one or two compartment body model. The efflux of MTX from the cerebrospinal fluid compartment is sufficiently significant to worsen myelosuppression, especially in 3-7 year old children. Therefore MTX cannot be administered intrathecally to such young children unless the complete remission in the number of circulating granulocytes is achieved according to general rules.
6-Mercaptopurine (6-MP)-induced sodium azide--iodine reaction was adapted for determination of 6-MP in urine of four children treated with single oral doses of the drug in tablets. Open one-compartment body model was assumed, and first-order elimination rate constants (K) and biological half-life times (t0,5) were calculated, and their precision was determined by statistical treatment.