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PKP-014 Variability of exposure parameters of adults treated with high doses methotrexate
  1. P Montejano-Hervás,
  2. I Reyes-Torres,
  3. MD Aumente,
  4. F Franco-García,
  5. I Viguera-Guerra
  1. Hospital Universitario Reina Sofia, Farmacia Hospitalaria, Cordoba, Spain


Background In the current treatment of Non-Hodgkin’s lymphomas (NHLs) with high-dose methotrexate, the dose is calculated according to different protocols, regardless of patients’ pharmacokinetic variability.

Purpose To evaluate the variability of exposure to methotrexate in adult patients with NHL who received high-dose methotrexate (>1,000 mg/m²) in order to justify the need to individualise the dose and optimise the treatment.

Material and methods Retrospective observational study, between October 2007 and June 2014. We included 43 adult patients (27–77 years old) with NHLs who received 96 cycles of methotrexate. Patients were classified into two groups, patients who received 1,000 mg/m² over 24 h in accordance with the HYPERCYVAD protocol (group I) and those who received 1,500 mg/m² infused over 24 h, following the BURKIMAB-08 protocol (group II). Methotrexate was measured by a fluorescence polarisation immunoassay (TDx/FLx System) in plasma samples obtained at 2, 12, 23, 36, 42 and 60 h after the start of infusion. Methotrexate pharmacokinetics parameters were estimated by Nonlinear Least Squares Regression (software Abbott PKs). The target range of exposure was defined as ±20% of the average AUC value, considering the extreme values positioned outside ±40%.

Results In group I, the AUC was 471.05 ± 188.59 μM h (235.29–1,231.34), 52.18% of the patients showed values within the pre-specified target (376.84–565.26), and 21.74% showed extreme values (>659.47 and <282.63). In group II, the AUC was 560.77 ± 194.63 μM h (308.53–1,414.62); 58% of patients showed values within the pre-specified target (448.62–672.93), and 16% showed extreme values (>785.08 and <336.46). The variability of the clearance in these patients (90.04 ± 30.59 ml/min/m²) would explain these results.

Conclusion The variability of exposure to methotrexate (37.99%) justifies the need to individualise dosage to optimise treatment. This could prevent an extreme risk of inefficacy or toxicity in the 18.75% of patients who are outside the pre-specified target range.

References and/or acknowledgements No conflict of interest.

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