Pharmacological issues concerning olaparib capsule and tablet formulations in treating ovarian cancer: Are they really the same drug?

Abstract

Olaparib is a first-in-class PARP inhibitor that has demonstrated efficacy as maintenance therapy in patients with ovarian cancer. It has been approved as a capsule formulation and after the publication of data from SOLO2 study became available also as tablet formulation. Due to different pharmacokinetic properties, these different formulations cannot be considered bioequivalent nor interchangeable. The tablet formulation has improved bioavailability, reducing pill burden and offering a more convenient dosage regimen. Furthermore, olaparib tablet formulation had a manageable tolerability profile if compared to capsule one, with most of adverse events of mild or moderate severity. Under this light, olaparib tablet formulation is a useful maintenance strategy for recurrent, platinum-sensitive ovarian cancer, providing a more convenient dosing option than the capsule formulation.

Identification of different side effects between PARP inhibitors and their polypharmacological multi‐target rationale

“…Talazoparib is the only PARPi that does not undergo hepatic metabolism and had the longest half‐life (90 h), 47 whereas olaparib had the shortest (15–11.9 h). The differences in behaviour of the tablet and capsule formulation of olaparib affects half‐life and clearance 48 …”

“…The differences in behaviour of the tablet and capsule formulation of olaparib affects half-life and clearance. 48 F I G U R E 1 Chemical structures of the four PARPi. The benzamide pharmacophore shared between the PARPi is highlighted in green.…”

Olaparib Outcomes in Patients with BRCA 1-2 Mutated, Platinum-Sensitive, Recurrent Ovarian Cancer in Croatia: A Retrospective Noninterventional Study

“…In Italian study, patients were initiated to 400 mg capsule formulation, while in SOLO2 patients received 300 mg tablets. Tablets and capsules have different pharmacokinetic properties and are not bioequivalent and interchangeable [15]. Tablets have better bioavailability and Mateo et al adaptive, phase 1 trial showed that the steady-state maximum plasma concentration and the area under the plasma concentration-time curve are higher in tablets of 250 mg than in capsules of 400 mg and that the patients' exposure after the 300 mg tablets even exceeded the exposure of 400 mg capsule [16].…”