Estimation of equipotent doses for anti-inflammatory effects of prednisolone and AZD9567, an oral selective non-steroidal glucocorticoid receptor modulator.

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 TNF alpha release, a biomarker of anti-inflammatory effect, measured in a lipopolysaccharide-stimulated whole bloodex vivoassay. Based on pharmacokinetic-pharmacodynamic models, TNF alpha 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 TNF alpha release of AZD9567 and prednisolone were well aligned with several other pro-inflammatory cytokines.