Effect of valproate on olanzapine plasma concentrations in patients with bipolar or schizoaffective disorder.
The effect of valproate on the steady-state plasma concentrations of olanzapine was investigated in 18 patients with bipolar or schizoaffective disorder. Additional valproate, at a dose ranging from 600 to 2000 mg/d, was administered for 4 weeks to patients stabilized on olanzapine (5-20 mg/d). During valproate coadministration, mean plasma olanzapine concentrations decreased significantly from 32.9 +/- 9.7 ng/mL at baseline to 27.4 +/- 9.8 ng/mL at week 2 (P = 0.02), and to 26.9 +/- 9.2 ng/mL at week 4 (P = 0.001). Smoking also decreased plasma olanzapine concentrations. Valproate coadministration with olanzapine was well tolerated and no patient showed a worsening of his or her psychopathological condition. These findings indicate that valproate, at doses of up to 2000 mg/d, is associated with a minimal, presumably not clinically significant, decrease in plasma olanzapine concentrations, possibly as a result of induction of olanzapine metabolism. New studies are needed to confirm that valproate could have mild inductive effects.
Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina and IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy. espina@unime.it
Edoardo
E
Spina
Concetta
C
D'Arrigo
Vincenza
V
Santoro
Maria Rosaria
MR
Muscatello
Gianluca
G
Pandolfo
Rocco
R
Zoccali
Francisco J
FJ
Diaz
Jose
J
de Leon
D000328:Adult; D000375:Aging; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D018687:Antidepressive Agents, Second-Generation / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001569:Benzodiazepines / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011618:Psychotic Disorders / Q000097:blood* / Q000188:drug therapy; D012907:Smoking; D013997:Time Factors; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
D000927:Anticonvulsants; D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D014635:Valproic Acid; D000077152:Olanzapine