Estimation of Equipotent Doses for Anti‐Inflammatory Effects of Prednisolone and AZD9567, an Oral Selective Nonsteroidal 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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-08-01
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| Series: | CPT: Pharmacometrics & Systems Pharmacology |
| Online Access: | https://doi.org/10.1002/psp4.12536 |
| _version_ | 1828497918770806784 |
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| author | Joachim Almquist Muhammad Waqas Sadiq Ulf G. Eriksson Tove Hegelund Myrbäck Susanne Prothon Jacob Leander |
| author_facet | Joachim Almquist Muhammad Waqas Sadiq Ulf G. Eriksson Tove Hegelund Myrbäck Susanne Prothon Jacob Leander |
| author_sort | Joachim Almquist |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T12:56:18Z |
| format | Article |
| id | doaj.art-af7419d539c84e809928c515313afae5 |
| institution | Directory Open Access Journal |
| issn | 2163-8306 |
| language | English |
| last_indexed | 2024-12-11T12:56:18Z |
| publishDate | 2020-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | CPT: Pharmacometrics & Systems Pharmacology |
| spelling | doaj.art-af7419d539c84e809928c515313afae52022-12-22T01:06:34ZengWileyCPT: Pharmacometrics & Systems Pharmacology2163-83062020-08-019844445510.1002/psp4.12536Estimation of Equipotent Doses for Anti‐Inflammatory Effects of Prednisolone and AZD9567, an Oral Selective Nonsteroidal Glucocorticoid Receptor ModulatorJoachim Almquist0Muhammad Waqas Sadiq1Ulf G. Eriksson2Tove Hegelund Myrbäck3Susanne Prothon4Jacob Leander5Clinical Pharmacology and Quantitative Pharmacology Clinical Pharmacology and Safety Sciences R&D, AstraZeneca Gothenburg SwedenClinical Pharmacology and Quantitative Pharmacology Clinical Pharmacology and Safety Sciences R&D, AstraZeneca Gothenburg SwedenClinical Pharmacology and Quantitative Pharmacology Clinical Pharmacology and Safety Sciences R&D, AstraZeneca Gothenburg SwedenClinical Pharmacology and Quantitative Pharmacology Clinical Pharmacology and Safety Sciences R&D, AstraZeneca Gothenburg SwedenClinical Pharmacology and Quantitative Pharmacology Clinical Pharmacology and Safety Sciences R&D, AstraZeneca Gothenburg SwedenClinical Pharmacology and Quantitative Pharmacology Clinical Pharmacology and Safety Sciences R&D, AstraZeneca Gothenburg SwedenAZD9567 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.https://doi.org/10.1002/psp4.12536 |
| spellingShingle | Joachim Almquist Muhammad Waqas Sadiq Ulf G. Eriksson Tove Hegelund Myrbäck Susanne Prothon Jacob Leander Estimation of Equipotent Doses for Anti‐Inflammatory Effects of Prednisolone and AZD9567, an Oral Selective Nonsteroidal Glucocorticoid Receptor Modulator CPT: Pharmacometrics & Systems Pharmacology |
| title | Estimation of Equipotent Doses for Anti‐Inflammatory Effects of Prednisolone and AZD9567, an Oral Selective Nonsteroidal Glucocorticoid Receptor Modulator |
| title_full | Estimation of Equipotent Doses for Anti‐Inflammatory Effects of Prednisolone and AZD9567, an Oral Selective Nonsteroidal Glucocorticoid Receptor Modulator |
| title_fullStr | Estimation of Equipotent Doses for Anti‐Inflammatory Effects of Prednisolone and AZD9567, an Oral Selective Nonsteroidal Glucocorticoid Receptor Modulator |
| title_full_unstemmed | Estimation of Equipotent Doses for Anti‐Inflammatory Effects of Prednisolone and AZD9567, an Oral Selective Nonsteroidal Glucocorticoid Receptor Modulator |
| title_short | Estimation of Equipotent Doses for Anti‐Inflammatory Effects of Prednisolone and AZD9567, an Oral Selective Nonsteroidal Glucocorticoid Receptor Modulator |
| title_sort | estimation of equipotent doses for anti inflammatory effects of prednisolone and azd9567 an oral selective nonsteroidal glucocorticoid receptor modulator |
| url | https://doi.org/10.1002/psp4.12536 |
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