Histamine H1-receptor antagonists, promethazine and homochlorcyclizine, increase the steady-state plasma concentrations of haloperidol and reduced haloperidol.
The effects of histamine H1-receptor antagonists, promethazine and homochlorcyclizine, both of which are inhibitors of CYP2D6, on the steady-state plasma concentrations (Css) of haloperidol and reduced haloperidol were studied in 23 schizophrenic inpatients receiving haloperidol, 12 to 36 mg/d, for 2 to 29 weeks. Promethazine, 150 mg/d, in 11 patients and homochlorcyclizine, 60 mg/d, in the others were coadministered for at least 1 week. Blood sampling was performed before and during coadministration of promethazine or homochlorcyclizine and 1 week after the discontinuation, together with clinical assessments by Brief Psychiatric Rating Scale (BPRS) and Udvalg for kliniske undersogelser (UKU) side effect rating scale. The Css (mean +/- SD) of haloperidol and reduced haloperidol during promethazine coadministration (27.6 +/- 24.9 and 8.6 +/- 13.2 ng/mL) were significantly higher than those before the coadministration (12.7 +/- 10.8 and 5.0 +/- 6.0 ng/mL; P < 0.01) or 1 week after the discontinuation (15.6 +/- 14.8 and 5.8 +/- 7.9 ng/mL; P < 0.05). The Css of haloperidol and reduced haloperidol during homochlorcyclizine coadministration (14.9 +/- 8.1 and 6.4 +/- 5.4 ng/mL) were also significantly higher than those before the coadministration (10.9 +/- 7.2 and 3.8 +/- 3.6 ng/mL; P < 0.01) or 1 week after the discontinuation (12.9 +/- 7.4 and 4.8 +/- 4.1 ng/mL; P < 0.05). No change in BPRS or UKU score was found throughout the study. Thus, the current study suggests that coadministration of clinical doses of promethazine and homochlorcyclizine increases the Css of haloperidol and reduced haloperidol via the inhibitory effects on the CYP2D6-catalyzed metabolism of haloperidol and reduced haloperidol.
T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T22 T23 T24 T25 T26 T27 T28 T29 T2 T30 T31 T3 T4 T5 T6 T7 T8 T9
CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-Y CHEMICAL GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
haloperidol haloperidol haloperidol haloperidol Promethazine homochlorcyclizine promethazine promethazine homochlorcyclizine homochlorcyclizine haloperidol haloperidol haloperidol promethazine Histamine haloperidol haloperidol promethazine homochlorcyclizine CYP2D6 histamine H1-receptor haloperidol CYP2D6 Histamine H1-receptor homochlorcyclizine histamine promethazine homochlorcyclizine haloperidol haloperidol haloperidol