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Life sciences · Journal article
Frontiers in Pharmacology · September 4, 2026
Encouraging direction, but not yet definitive.
This study presents a PBPK-VBE modeling framework to predict bioequivalence of senaparib 10 mg and 20 mg capsule strengths across the 20–80 mg dose range, where direct clinical studies are impractical due to nonlinear pharmacokinetics. Simulations across varied conditions (sample size, variability, prandial state) showed geometric mean ratios consistently near 100%, supporting the plausibility of bioequivalence bridging. However, this remains model-based evidence without in vivo confirmation at the lower doses.
Physiologically based pharmacokinetic modeling with virtual bioequivalence analysis. Senaparib capsule formulations (10 mg and 20 mg strengths) in the context of maintenance therapy for advanced ovarian cancer; simulated dosing across 20–80 mg range.. Intervention: Senaparib 20 mg capsule strength (composed of two 10 mg capsules) across 20–80 mg dose range, modeled via PBPK-VBE.. Compared with: Senaparib 10 mg capsule strength across 20–80 mg dose range..
Geometric mean ratios (GMRs) of key pharmacokinetic parameters consistently approached 100% across all evaluated conditions, including variations in sample size, intra-individual variability, and prandial states (fasted and fed). Bioequivalence demonstrated across the 20–80 mg dose range via PBPK-VBE modeling bridging from the clinical starting dose (100 mg, where conventional clinical BE was established) to the linear pharmacokinetic range.
Nonlinear pharmacokinetics of senaparib may limit extrapolation validity across the full dose range without in vivo confirmation. Geometric mean ratios (GMRs) of key pharmacokinetic parameters consistently approached 100% across all evaluated conditions, including variations in sample size, intra-individual variability, and prandial states (fasted and fed).
If validated clinically, this PBPK-VBE approach could support regulatory acceptance of dose strength bridging without requiring in vivo bioequivalence studies at each lower dose level, streamlining formulation development for drugs with nonlinear pharmacokinetics. Clinicians should note this remains predictive; actual clinical pharmacokinetics at 20–80 mg doses require confirmation.
A sound methodological approach (PBPK-VBE modeling) applied to a regulatory question, but based on simulation and in vitro data without in vivo clinical confirmation across the lower dose range, making it supportive rather than definitive evidence.
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If validated clinically, this PBPK-VBE approach could support regulatory acceptance of dose strength bridging without requiring in vivo bioequivalence studies at each lower dose level, streamlining formulation development for drugs with nonlinear pharmacokinetics. Clinicians should note this remains predictive; actual clinical pharmacokinetics at 20–80 mg doses require confirmation.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Aims Senaparib (Sepalna®), a novel oral poly (adenosine diphosphate -ribose) polymerase (PARP) 1/2 inhibitor, was approved in China in 2025 as maintenance therapy for advanced ovarian cancer. The recommended starting dose is 100 mg once daily, which may be adjusted to 80 mg, 60 mg, or 40 mg to manage adverse events. While conventional bioequivalence (BE) clinical studies established equivalence between the 10 mg and 20 mg capsules strengths at the 100 mg dose level, these findings cannot be extrapolated to the lower dose range due to senaparib’s nonlinear pharmacokinetics and the current absence of definitive regulatory guidance for such scenarios. This study aimed to evaluate the bioequivalence between the 10 mg and 20 mg capsule strengths of senaparib, a drug exhibiting nonlinear pharmacokinetics, across the 20–80 mg dose range. Methods We developed and validated an integrated approach combining physiologically based pharmacokinetic (PBPK) modeling with in vitro dissolution data to evaluate virtual bioequivalence (VBE) between the two capsule strengths across the 20–80 mg dose range. Results Under all evaluated conditions including variations in sample size, intra-individual variability levels, and prandial states (fasted and fed), the geometric mean ratios (GMRs) of key pharmacokinetic (PK) parameters consistently approached 100%, thereby confirming bioequivalence across the specified dosing range. Conclusion This PBPK-VBE framework provides supportive evidence for bioequivalence bridging of senaparib capsule strengths across the linear dose range, illustrating the potential utility of this approach for formulation bridging when direct clinical BE studies across all dose levels are impractical.
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