Amir Hooshang Mohammadpour - Pharmaceutical Research Centre and School of Pharmacy, Department of Pharmacodinamy and Toxicology, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran
Mohsen Foroughipour - Department of Neurology, Faculty of Medicine, Ghaem Hospital, MUMS, Mashhad, Iran
Mahmoud Reza Azarpazhooh - Department of Neurology, Faculty of Medicine, Ghaem Hospital, MUMS, Mashhad, Iran
Mohammad Hasanzadeh Khayat - Department of Medicinal Chemistry, Pharmaceutical Research Centre and School of Pharmacy, MUMS, Mashhad, Iran
Saeed Rezaee - Department of Pharmaceutics, School of Pharmacy, Ahwaz University of Medical Sciences, Ahwaz, Iran
Tamara Aghebati - Pharmaceutical Research Centre and School of Pharmacy, Department of Pharmacodinamy and Toxicology, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran
Jamal Shamsara - Department of Biotechnology, School of Pharmacy, MUMS, Mashhad, Iran

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 ۲۵ 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 (۱۰.۳۵±۵.۷۷ vs. ۷.۷۰±۲.۶۳ ml/kg/h, P= ۰.۰۴۷). 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.

Acute mania, Clearance, Epilepsy, Pharmacokinetics, Valproic acid