Determinants of free serum valproate concentration: A prospective study in patients on divalproex sodium monotherapy

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dc.contributor.authorNasreddine, Wassim M.
dc.contributor.authorDirani, Maya M.
dc.contributor.authorAtweh, Samir F.
dc.contributor.authorMakki, Achraf
dc.contributor.authorBeydoun, Ahmad A.
dc.contributor.departmentNeurology
dc.contributor.facultyFaculty of Medicine (FM)
dc.contributor.institutionAmerican University of Beirut
dc.date.accessioned2025-01-24T12:07:32Z
dc.date.available2025-01-24T12:07:32Z
dc.date.issued2018
dc.description.abstractPurpose: To evaluate variables affecting the valproate (VPA) free fraction and develop an equation for computing free VPA concentration from total VPA concentration. Methods: Trough total and free VPA concentrations were collected from patients who participated in a prospective VPA monotherapy trial. All available paired data of trough total and free VPA concentrations were included. Significant variables from the univariate analysis were evaluated in a multivariate model. Results: A total of 902 concomitant total and free VPA concentrations were available. Multivariate analysis showed that total VPA concentration, age and gender were significantly associated with VPA free fraction. However, the effect size of total VPA concentration was substantially higher than that of gender and age. VPA free fraction remained stable at around 10% for total VPA concentration between 20 and 60 μg/mL with subsequent linear increases for higher concentration. A scatter plot correlating total and free VPA concentrations showed that a quadratic equation best fitted the data, accounting for 88% of the free VPA concentration variance. Conclusions: An increase in the total VPA concentration results in corresponding linear and non-linear rise in the VPA free fraction and free VPA concentration, respectively. The total daily dose of VPA should be increased in smaller increments whenever a total VPA concentration of 60 μg/mL is reached. When drug monitoring is needed, we recommend measuring the free VPA concentration. If this test is unavailable, and for patients with normal albumin levels, it can be predicted from the total VPA concentration using the generated equation. © 2018 British Epilepsy Association
dc.identifier.doihttps://doi.org/10.1016/j.seizure.2018.04.012
dc.identifier.eid2-s2.0-85046729653
dc.identifier.pmid29730272
dc.identifier.urihttp://hdl.handle.net/10938/31554
dc.language.isoen
dc.publisherW.B. Saunders Ltd
dc.relation.ispartofSeizure
dc.sourceScopus
dc.subjectAntiepileptic drugs
dc.subjectFree fraction
dc.subjectFree level
dc.subjectTherapeutic drug monitoring
dc.subjectValproate
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAge factors
dc.subjectAged
dc.subjectAnticonvulsants
dc.subjectChild
dc.subjectDose-response relationship, drug
dc.subjectDouble-blind method
dc.subjectDrug monitoring
dc.subjectEpilepsy
dc.subjectFemale
dc.subjectHumans
dc.subjectLinear models
dc.subjectMale
dc.subjectMiddle aged
dc.subjectModels, biological
dc.subjectMultivariate analysis
dc.subjectNonlinear dynamics
dc.subjectSex factors
dc.subjectValproic acid
dc.subjectYoung adult
dc.subjectCarbamazepine
dc.subjectPhenobarbital
dc.subjectPhenytoin
dc.subjectPrimidone
dc.subjectValproate semisodium
dc.subjectAnticonvulsive agent
dc.subjectAge
dc.subjectAlbumin blood level
dc.subjectArticle
dc.subjectCohort analysis
dc.subjectControlled study
dc.subjectDouble blind procedure
dc.subjectDrug blood level
dc.subjectEffect size
dc.subjectGender
dc.subjectHuman
dc.subjectLinear system
dc.subjectMaintenance drug dose
dc.subjectMajor clinical study
dc.subjectMathematical computing
dc.subjectMonotherapy
dc.subjectMulticenter study
dc.subjectPharmacokinetic parameters
dc.subjectPhase 1 clinical trial
dc.subjectPlots and curves
dc.subjectPriority journal
dc.subjectProspective study
dc.subjectRandomized controlled trial
dc.subjectUnivariate analysis
dc.subjectBiological model
dc.subjectBlood
dc.subjectClinical trial
dc.subjectDose response
dc.subjectNonlinear system
dc.subjectSex factor
dc.subjectStatistical model
dc.titleDeterminants of free serum valproate concentration: A prospective study in patients on divalproex sodium monotherapy
dc.typeArticle

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