This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Vasudev, K. Articles by Tayal, G. Search for Related Content PubMed PubMed Citation Articles by Vasudev, K. Articles by Tayal, G. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Bipolar Disorder Hazardous Substances DB VALPROIC ACID Social Bookmarking                         What's this?

Pharmacokinetics of valproic acid in patients with bipolar disorder

Saurendra Das

Department of Pharmacology, Lady Harding Medical College and Associated Hospitals, New Delhi, India

Utpal Goswami

Department of Psychiatry Lady Hardinge Medical College and Associated Hospitals New Delhi, 110001 India; shrink_42{at}hotmail.com

Girish Tayal

Department of Pharmacology, Lady Harding Medical College and Associated Hospitals, New Delhi, India

The pharmacokinetics of valproic acid (VPA) were studied in nine patients with bipolar disorder who were receiving VPA as prophylactic therapy, following the full daily dose (400–1500 mg), on which the patients had been maintained for at least the past 3 months. The data from our study showed that the pharmacokinetics of valproate followed a two compartment open model. A time lag of 1–2 h was observed in each patient, followed by rapid absorption, with the peak concentrations being recorded approximately 4 h after drug administration. The average 12 h trough concentration was found to be 54.73 ± 11.96 µg/ml. The plasma level decline was biphasic with a terminal half-life of 14.2 ± 6.39 h. Total plasma clearance was 0.095 ± 0.035 ml/min/kg. The steady-state apparent volume of distribution was found to be 0.11 ± 0.05 l/kg. A positive correlation (r= 0.69) was found between the dose (mg/kg) and steady-state serum concentration (Css) of VPA and all patients, except one, had their Css above 50 µg/ml. Most of the pharmacokinetic parameters in this study involving euthymic bipolar patients on long-term VPA monotherapy were found to be in agreement with those reported in literature on seizure disorder patients on similar regime; however, the plasma elimination half-life appears to be prolonged in bipolar patients.

Key Words: mania • pharmacokinetics • therapeutic range • valproate

Journal of Psychopharmacology, Vol. 15, No. 3, 187-190 (2001)
DOI: 10.1177/026988110101500305


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?