Effects of comedication on the serum levels of aripiprazole: evidence from a routine therapeutic drug monitoring service.
BACKGROUND
The objective of the study was to compare the serum concentrations of the atypical antipsychotic aripiprazole in monotherapy with the concentrations found during concomitant therapy with other drugs.


METHODS
Samples analyzed for aripiprazole by a liquid chromatography-mass spectrometry method in a routine therapeutic drug monitoring setting were collected consecutively.


RESULTS
Samples from 81 patients were included in the study. Comedication with the CYP3A4 inducer carbamazepine lowered the dose-adjusted aripiprazole concentration by 88%. Comedication with CYP2D6 inhibitors gave a mean concentration 44% higher than in the monotherapy group. Subjects comedicated with valproate had lower aripiprazole concentrations, while subjects comedicated with lamotrigine, citalopram/escitalopram and lithium had higher concentrations than the subjects in the monotherapy group.


CONCLUSIONS
Although the study is small and the results should be interpreted very cautiously, it indicates that comedication with drugs inhibiting or inducing CYP2D6 or CYP3A4 affects the serum concentrations of aripiprazole. The other findings should be considered as preliminary and have to be replicated in a larger setting before firm conclusions can be drawn.
Castberg
I
I
Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway. ingrid.castberg@stolav.no
Spigset
O
O
D000293:Adolescent; D000328:Adult; D000368:Aged; D018692:Antimanic Agents / Q000008:administration & dosage / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D000068180:Aripiprazole; D002220:Carbamazepine / Q000008:administration & dosage / Q000494:pharmacology; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D015363:Quinolones / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D014635:Valproic Acid / Q000494:pharmacology
D018692:Antimanic Agents; D014150:Antipsychotic Agents; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D010879:Piperazines; D015363:Quinolones; D002220:Carbamazepine; D014635:Valproic Acid; D000068180:Aripiprazole; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human