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.
Spina
Edoardo
E
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
D'Arrigo
Concetta
C
Santoro
Vincenza
V
Muscatello
Maria Rosaria
MR
Pandolfo
Gianluca
G
Zoccali
Rocco
R
Diaz
Francisco J
FJ
de Leon
Jose
J
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