%0 Journal Article
%T Population Pharmacokinetics of Methotrexate in Egyptian Children with Lymphoblastic Leukemia
%A Ehab Said EL Desoky
%A Mohamed H. Ghazal
%A Rajendra P. Singh
%A Omnia N. Abdelhamid
%A Hartmut Derendorf
%J Pharmacology & Pharmacy
%P 139-145
%@ 2157-9431
%D 2013
%I Scientific Research Publishing
%R 10.4236/pp.2013.42020
%X <span style=\"font-family:Verdana;\"> </span><span style=\"font-family:Verdana;\">Background: </span><span><span style=\"font-family:Verdana;\">Individualization of high dose regimen of methotrexate (MTX) in pediatric patients with acute lymphoblastic leukemia based on pharmacokinetic (PK) parameters can help in optimization of the dose and better control of the disease. Building up of a pharmacokinetic model can help dose optimization. </span><span style=\"font-family:Verdana;\">Objectives:</span> </span><span style=\"font-family:Verdana;\">A NONMEM based population (POP) PK model has been subsequently developed to evaluate the effect of demographics as covariates to address variability in pharmacokinetics of MTX. </span><span style=\"font-family:Verdana;\">Method:</span><span style=\"font-family:Verdana;\"> <span style=\"font-family:Verdana;\">Forty one patients (24 males &amp; 17 females) with ranges of age, body weight and height of 3</span></span><span> </span><span style=\"font-family:Verdana;\">-</span><span> </span><span style=\"font-family:Verdana;\">15 years, 13</span><span> </span><span style=\"font-family:Verdana;\">-</span><span> </span><span style=\"font-family:Verdana;\">54 kg and 100</span><span> </span><span style=\"font-family:Verdana;\">-</span><span> </span><span style=\"font-family:Verdana;\">177 cm respectively and diagnosed as acute lymphoblastic leukemia (ALL) were involved in the study. MTX was administered as i.v. infusion at a dose of 2</span><span> </span><span><span style=\"font-family:Verdana;\">gm/m</span><sup><span style=\"font-family:Verdana;\">2</span></sup><span style=\"font-family:Verdana;\"> over a period of two hour and its plasma concentrations were determined primarily at 24 hr post-dose to be utilized in the building-up of PK model.</span></span><span><span style=\"font-family:Verdana;\">The initial/prior estimates of volumes of central (V</span><sub><span style=\"font-family:Verdana;\">1</span></sub><span style=\"font-family:Verdana;\">) and peripheral compartments (V</span><sub><span style=\"font-family:Verdana;\">2</span></sub><span style=\"font-family:Verdana;\">) and clearance (CL) and inter-compartmental clearance (Q</span><sub><span style=\"font-family:Verdana;\">2</span></sub><span style=\"font-family:Verdana;\">) for MTX were extracted from literature. The inter-subject variability w</span></span><span style=\"font-family:Verdana;\">as</span><span><span style=\"font-family:Verdana;\"> estimated for V</span><sub><span style=\"font-family:Verdana;\">1</span></sub><span style=\"font-family:Verdana;\"> &amp;
%K Methotrexate
%K Population Pharmacokinetics
%K Leukemia
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=29701