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

AbstractAZD9567 is a potent and selective non ‐steroidal oral glucocorticoid receptor modulator. It is developed as an anti‐inflammatory drug with improved safety profile compared to 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 % CI: 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.

Source: CPT: Pharmacometrics and Systems Pharmacology - June 4, 2020 Category: Drugs & Pharmacology Authors: Joachim Almquist, Muhammad Waqas Sadiq, Ulf G Eriksson, Tove Hegelund Myrb äck, Susanne Prothon, Jacob Leander Tags: ARTICLE Source Type: research