Is a Clinical Trial With a Non‐Bioequivalent Batch Necessary? The Critical Role of Intrasubject Variability in Olaparib Formulation Bridging by <scp>PBPK</scp>
and AUC, whereas the counterpart model was unable to reproduce the observed intrasubject variability. Our findings indicated that the clinical non-BE data may not be necessary in all cases. In certain scenarios, validation against intrasubject variability may meet the dual objectives of capturing PK variability and confirming sensitivity within the absorption model. Using the final model, we demonstrated BE between adult and pediatric formulations of olaparib in adults and showed minimal food effect on its exposure in pediatrics.
Authors
- Diansong Zhou (ORCID: https://orcid.org/0000-0002-2673-1069)
- Elizabeth Lowe (ORCID: https://orcid.org/0000-0003-3573-7208)
- Jin Dong
- Sandy Hopkins
- Xavier Pépin (ORCID: https://orcid.org/0000-0002-2180-5452)
- Weifeng Tang (ORCID: https://orcid.org/0000-0002-8261-8116)
- Andrea Moir (ORCID: https://orcid.org/0009-0008-5905-6646)
Institutions
- AstraZeneca (South Korea) (KR)
- AstraZeneca (Australia) (AU)
- AstraZeneca (Netherlands) (NL)
- AstraZeneca (Singapore) (SG)
- AstraZeneca (Poland) (PL)
- AstraZeneca (Finland) (FI)
- AstraZeneca (United States) (US)
Publication Details
- Journal
- Clinical Pharmacology & Therapeutics
- Published
- 2026-04-14
- DOI
- https://doi.org/10.1002/cpt.70284
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00