title: Comparison of Valproic acid Clearance between Epileptic Patients and Patients with Acute Mania.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pharmaceutical Research Centre and School of Pharmacy, Department of Pharmacodinamy and Toxicology, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran.
authors.forename: Amir Hooshang
authors.initials: AH
authors.lastname: Mohammadpour
authors.forename: Mohsen
authors.initials: M
authors.lastname: Foroughipour
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Azarpazhooh
authors.forename: Mohammad Hasanzadeh
authors.initials: MH
authors.lastname: Khayat
authors.forename: Saeed
authors.initials: S
authors.lastname: Rezaee
authors.forename: Tamara
authors.initials: T
authors.lastname: Aghebati
authors.forename: Jamal
authors.initials: J
authors.lastname: Shamsara
keywords: Acute mania; Clearance; Epilepsy; Pharmacokinetics; Valproic acid