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Virtual Bioequivalence Assessment of Elagolix Formulations Using Physiologically Based Pharmacokinetic Modeling
Dwaipayan Mukherjee1, Mong-Jen Chen2, Xi Shao3
1Clinical Pharmacology, AbbVie, Inc., Building AP31-3, 1 North Waukegan Rd., North Chicago, Illinois, 60064, USA. dwaipayan.mukherjee@abbvie.com.
The AAPS Journal
|March 23, 2023
Summary
Physiologically based pharmacokinetic (PBPK) modeling and in vitro dissolution data demonstrated virtual bioequivalence for elagolix capsules. This approach avoided large studies and reduced drug exposure in healthy women.
Area of Science:
- Pharmacokinetics
- Drug Development
- Regulatory Science
Background:
- Elagolix is approved for endometriosis, with existing tablet formulations.
- Commercial elagolix combination products utilize capsule formulations.
- Dissimilar in vitro dissolution profiles necessitated bioequivalence assessment.
Purpose of the Study:
- To assess virtual bioequivalence between elagolix tablet and capsule formulations.
- To utilize physiologically based pharmacokinetic (PBPK) modeling for regulatory purposes.
- To support a bioequivalence waiver, avoiding extensive clinical trials.
Main Methods:
- Incorporation of in vitro dissolution data into a verified PBPK model.
- External validation of the PBPK model using existing bioequivalence study data.
- Simulation of virtual bioequivalence trials to compare elagolix formulations.
Main Results:
- The PBPK model successfully simulated virtual bioequivalence trials.
- Commercial elagolix capsules met bioequivalence criteria (0.80-1.25) compared to reference tablets.
- Demonstrated virtual bioequivalence using PBPK modeling and in vitro data.
Conclusions:
- PBPK modeling combined with in vitro dissolution data can effectively demonstrate virtual bioequivalence.
- This novel approach supports regulatory bioequivalence waivers, reducing the need for large clinical studies.
- Physiologically based pharmacokinetic modeling offers an efficient alternative for drug product assessment.
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