Pharmacokinetics of haloperidol and fluphenazine decanoates in chronic schizophrenia.
In a double-blind comparison of haloperidol decanoate and fluphenazine decanoate given 4-weekly for 60 weeks as maintenance therapy in 38 chronic schizophrenic in-patients, plasma haloperidol, fluphenazine and prolactin levels were measured at regular intervals by radioimmunoassay. After the first injection, the mean plasma haloperidol level was highest at week 1 and fell gradually towards week 4. Mean pre-dose haloperidol levels changed little after week 8. Results suggested an absorption half-life of 4 weeks, although, in three cases steady state was only achieved after 11 monthly injections. Steady state levels of both haloperidol and fluphenazine correlated highly with dose. In two sub-groups observed at steady state, both drugs produced a biphasic pattern of plasma drug concentration between injections, a rapid rise on day 1 followed by stable elevated levels and a gradual return to pre-injection concentration by the end of week 4. In the fluphenazine sub-group there was a second peak on day 7 and a steeper decline, so that the mean area-under-curve in week 4 was 64% of that in week 1. Drug injections at steady state induced an increase in prolactin secretion in all of the fluphenazine sub-group and in half of those receiving haloperidol. Plasma prolactin changes resembled those for drug concentrations, but differences in times of peaks on day 1 resulted in weak correlations. Fluphenazine appeared more potent than haloperidol in provoking prolactin secretion.
Wiles
D H
DH
Department of Clinical Research, Crichton Royal Hospital, Dumfries, Scotland, UK.
McCreadie
R G
RG
Whitehead
A
A
D000328:Adult; D000368:Aged; D001682:Biological Availability; D004311:Double-Blind Method; D005260:Female; D005476:Fluphenazine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000097:blood; D011863:Radioimmunoassay; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*
D011388:Prolactin; C033563:haloperidol decanoate; C011825:fluphenazine depot; D006220:Haloperidol; D005476:Fluphenazine