Comparison of Valproic acid Clearance between Epileptic Patients and Patients with Acute Mania

Mohammadpour, Amir Hooshang; Foroughipour, Mohsen; Azarpazhooh, Mahmoud Reza; Hasanzadeh Khayat, Mohammad; Rezaee, Saeed; Aghebati, Tamara; Shamsara, Jamal

doi:10.22038/ijbms.2011.5054

Comparison of Valproic acid Clearance between Epileptic Patients and Patients with Acute Mania

Document Type : Original Article

Authors

¹ Pharmaceutical Research Centre and School of Pharmacy, Department of Pharmacodinamy and Toxicology, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran

² Department of Neurology, Faculty of Medicine, Ghaem Hospital, MUMS, Mashhad, Iran

³ Department of Medicinal Chemistry, Pharmaceutical Research Centre and School of Pharmacy, MUMS, Mashhad, Iran

⁴ Department of Pharmaceutics, School of Pharmacy, Ahwaz University of Medical Sciences, Ahwaz, Iran

⁵ Department of Biotechnology, School of Pharmacy, MUMS, Mashhad, Iran

10.22038/ijbms.2011.5054

Abstract

Objective(s)
The purpose of this study was assessment of the influence of acute manic phase on the steady state pharmacokinetics of valproic acid (VPA) in bipolar patients in comparison with those of epileptic patients. Materials and Methods
Ninteen acutely manic and 25 epileptic patients who fulfilled inclusion and exclusion criteria were entered in this prospective study. Blood samples were collected at trough time in steady state and plasma concentrations were determined by fluorescence polarization immunoassay (FPIA). VPA apparent oral clearance (CL/F) values were calculated in each patient and were compared between groups. As VPA clearance is affected by different factors such as age, total body weight, VPA dosage and the use of concurrent medications, all of these confounding factors were made similar in both groups.
Results
Comparison between two groups showed that CL/F values in acutely manic patients were significantly higher than epileptic patients (10.35±5.77 vs. 7.70±2.63 ml/kg/h, P= 0.047).
Conclusion
Acutely manic patients require more VPA dosage to achieve serum concentrations in comparison with those found in epileptic patients. It may be suggested that this increased VPA clearance in acute manic phase may be related to abnormalities in membrane transport systems that may affect on cellular uptake of the drug and its volume of distribution. Since our study is a preliminary investigation in this field, further detailed pharmacokinetic study in acute manic patients are warranted to confirm results of this study.

Keywords

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