Relationship between Patient Demographic Characteristics, Valproic Acid Dosage and Clearance in Adult Iranian Patients

Document Type : Original Article


1 Pharmaceutical Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Neurology, Faculty of Medicine, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Psychiatry, Faculty of Medicine & Psychiatric Research Centre, Ebn-sina Hospital, Mashad University of Medical Sciences, Mashhad, Iran

4 Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Pharmacodinamy & Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran


As there are conflicting findings regarding the clearance-dose and patient characteristics relationships for valproic acid (VPA), this study was conducted to investigate the relationship between patient demographic characteristics, VPA dosage and the drug clearance in adult Iranian patients.
Materials and Methods
Patients (N= 47) were either on monotherapy with VPA or were under co-treatment with drugs that have no effect on VPA pharmacokinetic (PK) profile. All of the patients received VPA at therapeutic dose. Steady state trough plasma concentrations of VPA were determined by Fluorescence Polarization Immunoassay (FPIA) and VPA apparent clearance (CL/F) were calculated in each patient.
Mean VPA dose and VPA CL/F were 8.93±2.2 mg/kg/day and 0.65±0.55 l/hr respectively. No significant correlations were found between VPA CL/F and patients' age, TBW and VPA dose. VPA CL/F values of male and female patients were compared and no significant difference between these two groups was noted (P> 0.05). Significant correlation between VPA dose and total trough plasma concentration was found        (P= 0.001). Mean total VPA plasma concentration was 54.51±23.74 mg/l.
Our study showed PK of VPA was not affected by age, sex, TBW and VPA dose. However, for detailed results and construction of VPA PK model in Iranian patients, it is necessary to evaluate VPA PK in a larger sample size with different VPA doses, age and TBW ranges. 


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