Receptor occupancy theory-based analysis of interindividual differences in antiemetic effects of 5-HT3 receptor antagonists.
BACKGROUND
The aim of this study was to estimate interindividual differences in the antiemetic effects of 5-HT(3) receptor antagonists by evaluating the influence of pharmacokinetics on 5-HT(3) receptor occupancies, based on receptor occupancy theory.


METHODS
We analyzed interindividual differences of 5-HT(3) receptor occupancies and antiemetic effects after the oral and/or intravenous administration of standard doses of the following 5-HT(3) receptor antagonists: azasetron, granisetron, indisetron, ondansetron, ramosetron, and tropisetron.


RESULTS
The interindividual difference between maximum and minimum 5-HT(3) receptor occupancies after oral administration ranged from 0.6% to 64.0%, and that difference after intravenous administration ranged from 0.6% to 29.6%. Following oral administration, the interindividual difference between maximum and minimum complete vomiting inhibition rates ranged from 0.2% to 16.1%. After intravenous administration, that difference ranged from 0.8% to 52.5%.


CONCLUSIONS
Interindividual differences in the clinical effects of 5-HT(3) receptor antagonists could be evaluated based on receptor occupancy theory, and the differences varied among drugs. Drug selection considering these individual variations might be useful for the patients who experienced vomiting associated with chemotherapy.
Ayuhara
Hideaki
H
Department of Clinical Evaluation of Drug Efficacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Takayanagi
Risa
R
Okuyama
Kiyoshi
K
Yoshimoto
Koichi
K
Ozeki
Takeshi
T
Yokoyama
Haruko
H
Yamada
Yasuhiko
Y
D000932:Antiemetics / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001562:Benzimidazoles / Q000493:pharmacokinetics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D017829:Granisetron / Q000493:pharmacokinetics; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics; D008962:Models, Theoretical; D017294:Ondansetron / Q000493:pharmacokinetics; D010078:Oxazines / Q000493:pharmacokinetics; D058831:Serotonin 5-HT3 Receptor Antagonists; D016896:Treatment Outcome; D000077526:Tropisetron; D014839:Vomiting / Q000188:drug therapy
D000932:Antiemetics; D001562:Benzimidazoles; D019086:Bridged Bicyclo Compounds, Heterocyclic; D017829:Granisetron; D007211:Indoles; D017294:Ondansetron; D010078:Oxazines; D058831:Serotonin 5-HT3 Receptor Antagonists; D000077526:Tropisetron; C070671:azasetron; C071315:ramosetron