Predominant role of the 9-hydroxy metabolite of risperidone in elevating blood prolactin levels.
OBJECTIVE
The atypical antipsychotic risperidone significantly raises plasma prolactin levels in patients, but clozapine, olanzapine, and quetiapine do not. The differences in neuroendocrine response may be connected with the metabolism of the medications. The authors examined the contributory role of risperidone's active metabolite 9-hydroxy-risperidone by measuring plasma concentrations of risperidone, 9-hydroxy-risperidone, and prolactin.


METHODS
Blood samples taken from 25 patients with psychotic disorders following 6 weeks of treatment with risperidone (mean dose=3 mg/day) were examined. Mean plasma concentrations of risperidone, 9-hydroxy-risperidone, and prolactin were 4.6, 19.4, and 49.3 ng/ml, respectively.


RESULTS
The oral dose of risperidone correlated significantly with plasma concentrations of risperidone, 9-hydroxy-risperidone, active moiety, and prolactin. The plasma concentration of 9-hydroxy-risperidone, but not of risperidone, correlated significantly with increases in plasma prolactin.


CONCLUSIONS
These data suggest that the 9-hydroxy metabolite plays a predominant role in risperidone's effect on prolactin release.
Knegtering
Rikus
R
Department of Psychiatry, University Hospital Groningen, the Netherlands. H.Knegtering@psy.umcg.nl
Baselmans
Pepijn
P
Castelein
Stynke
S
Bosker
Fokko
F
Bruggeman
Richard
R
van den Bosch
Robert J
RJ
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006966:Hyperprolactinemia / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism*; D007555:Isoxazoles / Q000009:adverse effects / Q000378:metabolism* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D011388:Prolactin / Q000097:blood* / Q000378:metabolism; D011618:Psychotic Disorders / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D011743:Pyrimidines / Q000009:adverse effects / Q000378:metabolism* / Q000493:pharmacokinetics*; D018967:Risperidone / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use
D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D011388:Prolactin; D018967:Risperidone; D000068882:Paliperidone Palmitate