@article {Montejano-Herv{\'a}sA136, author = {P Montejano-Herv{\'a}s and I Reyes-Torres and MD Aumente and F Franco-Garc{\'\i}a and I Viguera-Guerra}, title = {PKP-014 Variability of exposure parameters of adults treated with high doses methotrexate}, volume = {22}, number = {Suppl 1}, pages = {A136--A137}, year = {2015}, doi = {10.1136/ejhpharm-2015-000639.329}, publisher = {BMJ Specialist Journals}, abstract = {Background In the current treatment of Non-Hodgkin{\textquoteright}s lymphomas (NHLs) with high-dose methotrexate, the dose is calculated according to different protocols, regardless of patients{\textquoteright} pharmacokinetic variability.Purpose To evaluate the variability of exposure to methotrexate in adult patients with NHL who received high-dose methotrexate (\>1,000 mg/m{\texttwosuperior}) 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{\textendash}77 years old) with NHLs who received 96 cycles of methotrexate. Patients were classified into two groups, patients who received 1,000 mg/m{\texttwosuperior} over 24 h in accordance with the HYPERCYVAD protocol (group I) and those who received 1,500 mg/m{\texttwosuperior} 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 {\textpm}20\% of the average AUC value, considering the extreme values positioned outside {\textpm}40\%.Results In group I, the AUC was 471.05 {\textpm} 188.59 μM h (235.29{\textendash}1,231.34), 52.18\% of the patients showed values within the pre-specified target (376.84{\textendash}565.26), and 21.74\% showed extreme values (\>659.47 and \<282.63). In group II, the AUC was 560.77 {\textpm} 194.63 μM h (308.53{\textendash}1,414.62); 58\% of patients showed values within the pre-specified target (448.62{\textendash}672.93), and 16\% showed extreme values (\>785.08 and \<336.46). The variability of the clearance in these patients (90.04 {\textpm} 30.59 ml/min/m{\texttwosuperior}) 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.}, issn = {2047-9956}, URL = {https://ejhp.bmj.com/content/22/Suppl_1/A136.4}, eprint = {https://ejhp.bmj.com/content/22/Suppl_1/A136.4.full.pdf}, journal = {European Journal of Hospital Pharmacy} }