-2%
Olaparib-
Breast Cancer:
Ovarib is approved as monotherapy for adult patients with HER2-negative metastatic breast cancer harboring confirmed or suspected harmful germline BRCA mutations (gBRCAm). Candidates should have previously undergone chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. For hormone receptor-positive cases, disease progression during or unsuitability for endocrine therapy must be confirmed.
Ovarian Cancer:
Indicated for maintenance therapy in adult patients with platinum-sensitive relapsed (PSR) high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who have achieved a complete or partial response to platinum-based chemotherapy.
Olaparib is a PARP (poly ADP-ribose polymerase) enzyme inhibitor targeting PARP1, PARP2, and PARP3, which are involved in DNA repair, transcription, and cell cycle control. Inhibiting these enzymes, particularly in BRCA-deficient cells, induces DNA damage and promotes the death of cancer cells. Preclinical studies demonstrate tumor suppression in models both alone and after platinum chemotherapy.
Absorption: Rapid; peak levels in 1–3 hours post-dose. High-fat meals delay peak time by ~2 hours but only modestly increase overall exposure (~20% increase in AUC).
Distribution: Mean volume of distribution ~167 L. Plasma protein binding ~82%.
Metabolism: Mainly via CYP3A4/5. The majority of the circulating drug is unchanged Olaparib. Extensively metabolized to oxidized and conjugated forms.
Excretion: Half-life ~12 hours. ~44% eliminated via urine and 42% via feces, mostly as metabolites.