Pharmacokinetics of aripiprazole and concomitant lithium and valproate.
The objective of this study was to assess the pharmacokinetics of the antipsychotic aripiprazole when coadministered with lithium or valproate. Two open-label, sequential treatment design studies were conducted in chronically institutionalized patients with schizophrenia or schizoaffective disorder requiring treatment with lithium (n = 12) or valproate (divalproex sodium) (n = 10). Patients received aripiprazole 30 mg/day on days 1 to 14 and aripiprazole with concomitant therapy on days 15 to 36. Lithium was titrated from 900 mg until serum concentrations reached 1.0 to 1.4 mEq/L for at least 5 days. Valproate was titrated to 50 to 125 mg/L. Coadministration with lithium increased mean Cmax and AUC values of aripiprazole by about 19% and 15%, respectively, whereas the apparent oral clearance decreased by 15%. There was no effect on the steady-state pharmacokinetics of the active metabolite of aripiprazole. Coadministration with valproate decreased the AUC and Cmax of aripiprazole by 24% and 26%, respectively, with minimal effects on the active metabolite. Therapeutic doses of lithium and divalproex had no clinically significant effects on the pharmacokinetics of aripiprazole in patients with schizophrenia or schizoaffective disorder.
Citrome
Leslie
L
Nathan S. Kline Institute for Psychiatic Research and the Rockland Psychiatric Center, Orangeburg, NY 10962, USA.
Josiassen
Richard
R
Bark
Nigel
N
Salazar
Daniel E
DE
Mallikaarjun
Suresh
S
D000328:Adult; D000068180:Aripiprazole; D004359:Drug Therapy, Combination; D006801:Humans; D008094:Lithium / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy; D015363:Quinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy; D014635:Valproic Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D010879:Piperazines; D015363:Quinolones; D014635:Valproic Acid; D000068180:Aripiprazole; D008094:Lithium