Estimation of Equipotent Doses for Anti-Inflammatory Effects of Prednisolone and AZD9567, an Oral Selective Nonsteroidal Glucocorticoid Receptor Modulator.
CPT Pharmacometrics Syst Pharmacol
; 9(8): 444-455, 2020 08.
Article
en En
| MEDLINE
| ID: mdl-32501650
ABSTRACT
AZD9567 is a potent and selective nonsteroidal oral glucocorticoid receptor modulator. It is developed as an anti-inflammatory drug with improved safety profile compared with steroids like prednisolone. Throughout the clinical development of AZD9567, dose selection and data interpretation require a method for determining doses with the same anti-inflammatory effect as prednisolone. Equipotent doses of AZD9567 and prednisolone were defined by the same average inhibition of TNFα release, a biomarker of anti-inflammatory effect, measured in a lipopolysaccharide-stimulated whole blood ex vivo assay. Based on pharmacokinetic-pharmacodynamic models, TNFα dose-response relationships for AZD9567 and prednisolone were established. A comparison of the dose-response curves enabled estimation of an equipotency relationship. Specifically, 20 mg prednisolone was estimated to be equipotent to 40 mg AZD9567 (95% confidence interval 29-54 mg). Static concentration-response analyses showed that the relative potencies for inhibition of TNFα release of AZD9567 and prednisolone were well aligned with several other pro-inflammatory cytokines.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Piridinas
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Prednisolona
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Indazoles
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Antiinflamatorios
/
Modelos Biológicos
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
CPT Pharmacometrics Syst Pharmacol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Suecia