Receptor occupancy theory-based analysis of antiemetic effects and standard doses of 5-HT3 receptor antagonists in cancer patients.
Cancer Chemother Pharmacol
; 54(2): 185-90, 2004 Aug.
Article
em En
| MEDLINE
| ID: mdl-15168080
ABSTRACT
PURPOSE:
The aim of this study was to determine the usefulness of receptor occupancy theory-based analysis using pharmacokinetic and pharmacodynamic parameters for predicting the average receptor occupancy (PhiB) in humans of each of five 5-HT3 antagonists administered at standard doses.METHODS:
The relationship between the PhiB value and the complete vomiting inhibition rate after a single intravenous administration of cisplatin (not less than 50 mg/m2) was analyzed.RESULTS:
The predicted PhiB values after intravenous administration and oral administration of 5-HT3 antagonists were more than 65% and 50%, respectively, suggesting that relatively high receptor occupancy is required to elicit sufficient antiemetic effects of 5-HT3 antagonists. Moreover, significant ( P<0.05) linear relationships were found between PhiB values and complete vomiting inhibition rates of 5-HT3 antagonists in preventive cisplatin therapy, with correlation coefficients higher than 0.9, suggesting that the 5-HT3 receptor occupancy is an appropriate index of clinical efficacy of 5-HT3 antagonists, with higher receptor occupancy indicating more extensive antiemetic action.CONCLUSION:
The receptor occupancy theory-based analysis of the antiemetic effect of a 5-HT3 receptor antagonist used in this study should be very useful for not only estimating a rational dosage regimen but also determining the standard dose of a new drug using experimental data obtained in a preclinical study.
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Base de dados:
MEDLINE
Assunto principal:
Receptores 5-HT3 de Serotonina
/
Antagonistas do Receptor 5-HT3 de Serotonina
/
Modelos Teóricos
/
Antieméticos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article