In humans, 2-fluoro-ara-AMP rapidly and completely dephosphorylated to the nucleoside 2-fluoro-ara-A. After a single infusion to patients with stanozolol dosage maximum concentration of 2-fluoro-ara-A is 3.5-3.7 mol and reached the end of infusion . Determine the appropriate level of 2-fluoro-ara-A after five injections of the drug showed moderate cumulation with a mean Cmax equal to 4.4-4.8 mmol at the time of the end of infusion. During the five-day treatment levels of 2-fluoro-ara-A in the plasma increased in two times. Thus accumulation of 2-fluoro-ara-A after several treatment cycles may be small. Communication 2-fluoro-ara-A plasma proteins – small. After reaching plasma levels of 2-fluoro-ara-A is reduced in three phases: elimination in the alpha phase is about 5 minutes, the beta phase and 1.2 hours in the terminal phase of about 20 hours.
2-fluoro-ara-A excreted mainly by the kidneys (40-60% of the administered I / dose). 2-fluoro-ara-A is delivered to the leukemic cells active transport where refosforiliruetsya to partially monophosphate to the triphosphate and da. Triphosphate is the major intracellular metabolite and the only known metabolite possessing cytotoxic activity. The maximum concentration of in leukemic lymphocytes from patients was observed after an average of 4 hours after andriol kopen the infusion and characterized by significant fluctuations average value of about 20 micromolar. The concentration in leukemic cells was always much higher than its maximum concentration in the plasma, indicating that the cumulation of material in the target cells.
A clear correlation between the pharmacokinetics of 2-fluoro-ara-A and the therapeutic effect of the drug in cancer patients have been identified, however, the frequency of neutropenia and changes in hematocrit indicate the dose-dependent cytotoxic effect of fludarabine phosphate as hematopoietic suppression.
Individuals with impaired renal function was observed reduction of the total clearance of the drug, indicating the need for dose reduction.
- B-cell lymphocytic leukemia stanozolol dosage.
- Non-Hodgkin’s lymphoma.
- Increased sensitivity to fludarabine or other components of the preparation.
- Impaired renal function (creatinine clearance less than 30 mL / min).
- Decompensated haemolytic anemia.
- Pregnancy and lactation.
- Children’s age (lack of sufficient clinical data)
Precautions: after a careful assessment of risk / benefit ratio fludarabine should be used in frail patients with marked decrease in bone marrow function (thrombocytopenia, anemia and / or granulocytopenia), in patients with renal or hepatic insufficiency, immunodeficiency, opportunistic infections in history, in patients older than 75 years.
Dosage and administration
are allowed only in / in the introduction of fludarabine, so as to avoid accidental extravascular hit.
recommended dose fludarabine phosphate is 25 mg / m2 body surface / w once a day for 5 days every 28 days. The required dose (calculated in accordance with the patient’s body surface area) in a syringe.For I / bolus dose of the above formulation was diluted in 10 ml of 0.9% sodium chloride solution as required dose can be diluted in 100 ml 0.9% sodium chloride and administered kapelyyu for 30 minutes.There are no clear data on the optimal duration of treatment is not. The course of treatment depends on the observed effect and tolerability.
It is recommended that treatment with fludarabine to achieve a therapeutic response (usually 6 cycles), after the drug overturned.
Use in patients with impaired hepatic function
on the efficacy and safety data of fludarabine in patients with impaired hepatic function is limited. Patients in this group fludarabine administered with caution after a careful assessment of risk / benefit ratio.Treatment of these patients should be under close supervision. It may be necessary to reduce the dose or cancel treatments.
Use in patients with impaired renal function
In patients with possible impaired renal function and in patients older than 70 years is necessary to determine the creatinine clearance. If creatinine clearance in the range of 30-70 ml / min the dose should be reduced by up to 50%, and controlled to treat blood tests to assess toxicity. If creatinine stanozolol dosage clearance less than 30 mL / min fludarabine treatment is contraindicated.
The frequency of adverse events listed based on clinical trial data regardless of the causal relationship with fludarabine, in accordance with the following gradation of frequency: very common (more than 10%), common (more than 1% but less than 10%), uncommon (more than 0.1% but less than 1%), rare (more than 0.01% but less than 0.1%).