title: Pharmacokinetics of valproic acid in patients with bipolar disorder.
abstract: 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 microg/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 microg/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.
authors.affiliation: Department of Pharmacology, Lady Harding Medical College and Associated Hospitals, New Delhi, India.
authors.forename: K
authors.initials: K
authors.lastname: Vasudev
authors.forename: S
authors.initials: S
authors.lastname: Das
authors.forename: U
authors.initials: U
authors.lastname: Goswami
authors.forename: G
authors.initials: G
authors.lastname: Tayal
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D018692:Antimanic Agents; D014635:Valproic Acid