title: Relationships between pharmacokinetic parameters of carbamazepine and therapeutic response in patients with bipolar disease.
abstract: This study aimed to assess the relationship between plasma levels of carbamazepine and its active metabolite 10,11-epoxide-carbamazepine, and the therapeutic response in patients with bipolar disease. Thirteen patients were kept on a fixed individual dose of carbamazepine for 19 weeks under psychiatric care. Steady-state plasma concentrations of carbamazepine and its metabolite 10,11-epoxide-carbamazepine were measured at weeks 4, 12, and 20 by HPLC essay. Simultaneously, the psychopathologic state was assessed using the Brief Psychiatric rating scale (BPRS). Upon correlational analysis, mean BPRS scores did not correlate with the plasma levels of carbamazepine, whereas both mean plasma levels of 10, 11-epoxide-carbamazepine concentrations and 10,11-epoxide-carbamazepine to plasma carbamazepine ratio were closely correlated with mean values of BPRS scores (r = 0.80, p =10(-4), r= -0.89, p =10(-3) respectively). Optimum therapeutic response was observed among patients who had a plasma metabolite level of 1.4 μg/mL and a plasma carbamazepine concentrations of 7 μg/mL simultaneously. These results suggest that both plasma carbamazepine and 10,11-epoxide-carbamazepine levels must be fixed to achieve optimum therapeutic response. In order to reach these conditions, inhibitor drugs (such as valproic acid) or inductor drugs (such as phenobarbital) of epoxyde-hydrolase might be coadministered with the carbamazepine in order to adapt the plasma level of 10,11-epoxide-carbamazepine.
authors.affiliation: Laboratory of metabolic biophysics, Professional and applied environmental toxicology, Department of biophysics, Medicine faculty of Sousse, University of Sousse, Tunisia.
authors.forename: Chahra
authors.initials: C
authors.lastname: Chbili
authors.affiliation: Psychiatry department, Central hospital university (CHU), Sousse, Tunisia.
authors.forename: Souhail
authors.initials: S
authors.lastname: Bannour
authors.affiliation: Laboratory of metabolic biophysics, Professional and applied environmental toxicology, Department of biophysics, Medicine faculty of Sousse, University of Sousse, Tunisia.
authors.forename: Saida
authors.initials: S
authors.lastname: Khlifi
authors.affiliation: Psychiatry department, Central hospital university (CHU), Sousse, Tunisia.
authors.forename: Bechir
authors.initials: B
authors.lastname: Ben Hadj Ali
authors.affiliation: Laboratory of metabolic biophysics, Professional and applied environmental toxicology, Department of biophysics, Medicine faculty of Sousse, University of Sousse, Tunisia.
authors.forename: Saad
authors.initials: S
authors.lastname: Saguem
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000097:blood / Q000188:drug therapy*; D002220:Carbamazepine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D018692:Antimanic Agents; D002220:Carbamazepine
keywords: 10; 11-epoxide-carbamazepine; BPRS; HPLC; bipolar disorder; carbamazepine