Effect of dose timing in relation to food intake on systemic exposure to blonanserin.
OBJECTIVE
Blonanserin is a novel potent dopamine D(2) and serotonin 5-HT(2) antagonist for treating schizophrenia. The aim of this study was to investigate prandial effects on systemic exposure to blonanserin in healthy volunteers, with particular attention paid to the effect of dose timing relative to meal intake.


METHODS
Volunteers received a single 2-mg oral dose of blonanserin under the following conditions: fasting, 30 min before eating a standard meal; or 30 min or 2 or 4 h after eating the meal. Plasma concentrations of blonanserin were measured using validated high-performance liquid chromatography coupled with tandem mass spectrometry.


RESULTS
Ratios and 90% confidence intervals of the geometric means compared with the fasting condition indicated that the maximum concentrations of blonanserin (C(max)) significantly increased with dosing 30 min before meal intake, and 30 min and 2 and 4 h after meal intake, yielding by 330%, 239%, 272%, and 138%, respectively. The truncated area under the concentration-time curve (AUC(last)) also increased by 386%, 201%, 256%, and 155%, respectively. There was no difference in values of the time to reach maximum concentration between the fasting and the four fed states.


CONCLUSIONS
Food intake increased the systemic exposure to blonanserin for all time intervals investigated in this study. The marked effect of food on the bioavailability of blonanserin should be taken into account in its dosing schedules.
Saruwatari
Junji
J
Department of Neuropsychiatry, Hirosaki University School of Medicine, 5 Zaifucho, Hirosaki 036-8562, Japan.
Yasui-Furukori
Norio
N
Inoue
Yoshimasa
Y
Kaneko
Sunao
S
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D001682:Biological Availability; D015986:Confounding Factors, Epidemiologic; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004435:Eating; D005215:Fasting; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D010879:Piperazines / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology*; D010880:Piperidines / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology*; D019518:Postprandial Period; D012016:Reference Values; D012107:Research Design; D013997:Time Factors
D010879:Piperazines; D010880:Piperidines; C079310:blonanserin