Pharmacokinetics of High-Dose Methotrexate in Egyptian Children with Acute Lymphoblastic Leukemia: Impact of Interpatient Variations
Journal Title: IOSR Journal of Pharmacy (IOSRPHR) - Year 2015, Vol 5, Issue 10
Abstract
Aim:Since several factors have been shown to influence the clearance of methotrexate, the purpose of this study was to identify potential relationships between patient covariates and the methotrexate clearance estimates and deduce a pharmacokinetic model for the estimation of methotrexate clearance in Egyptian pediatric ALL patients that may help dosage adjustment and achieve target steady-state plasma concentrations in a similar sittings. Patients and methods: A total of 94 pediatric patients with B-cell ALL, of whom 70 were the studied population and 24 were the test population, were treated with four courses of HDMTX doses 2.5 gm/m2 (low-risk arm) or 5 gm/m2 (standard-/high-risk arm) given every other week by intermittent intravenous infusions over 24 hours as a part of their treatment protocol. Patients were monitored for the 24 hour MTX concentration and the systemic methotrexate clearance was calculated for each methotrexate dose. Results:The studied patients had average age of 7.1 ± 4.44 years; total body weight of 30.3 ± 21.04 kg, average height of 117.63 ± 28.09 cm, body surface area of 0.97 ± 0.45 m2 and body mass index of 19.25 ± 4.49. The average creatinine clearance calculated using Schwartz formula was 167.83 ± 48.44 ml/min. The mean methotrexate clearance was 7.83 ± 4.52 L/hr. Estimated creatinine clearance and body mass index were identified as the most important factors influencing methotrexate clearance in the studied patients. Conclusion:A Pharmacokinetic model was proposed to estimate the individual methotrexate clearance for Egyptian pediatric ALL patients. The derived final regression model reasonably predicted clearance values with best fitness and precessions
Authors and Affiliations
Abdel-Hameed I. M. Ebid1,Mohamed A. M. Ibrahim1 , Sameera Ezzat2
Keywords
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