{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:15:56Z","timestamp":1789676156692,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2008,12,8]],"date-time":"2008-12-08T00:00:00Z","timestamp":1228694400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Background<\/jats:italic>. The aim of this study was to determine the factors that influence valproate clearance (<jats:italic>CL<\/jats:italic>) in Mexican epileptic pediatric patients using a mixed\u2010effect model and sparse data of serum concentrations of valproic acid (VPA) collected during routine clinical care of patients.<\/jats:p><jats:p><jats:italic>Methods.<\/jats:italic> The number of patients included in the study was 110. The population <jats:italic>CL<\/jats:italic> was calculated by using the NONMEM program. The following covariates were tested by their influence on <jats:italic>CL<\/jats:italic>: total body weight (TBW), height, age, body surface area, daily dose (DD), sex of the patient and comedication with phenobarbital (PB) or carbamazepine.<\/jats:p><jats:p><jats:italic>Results.<\/jats:italic> The final regression model for valproic <jats:italic>CL<\/jats:italic> found best to describe the data was: <jats:italic>CL<\/jats:italic>\/<jats:italic>F<\/jats:italic>=(0.0466+0.00363 <jats:italic>TBW<\/jats:italic>+0.000282 <jats:italic>DD<\/jats:italic>) <jats:sup>*<\/jats:sup> (1+0.236 <jats:italic>PB<\/jats:italic>). This model allows a reduction of 50% of the interindividual variability and of 31% of the residual variability described by the basic model that does not include covariables.<\/jats:p><jats:p><jats:italic>Conclusions.<\/jats:italic> Total body weight, daily dose of valproate and concomitant therapy with PB are factors that significantly influence VPA kinetic disposition and they should be considered in programming dosage regimens for this antiepileptic drug in the pediatric population. The validation of the model supports its acceptability for clinical purposes. 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