PURPOSE: The poly(ADP-ribose) polymerase inhibitor rucaparib is approved for the treatment of patients with recurrent ovarian and metastatic castration-resistant prostate cancer; however, limited data are available on its use in patients with hepatic dysfunction. This study investigated whether hepatic impairment affects the pharmacokinetics, safety, and tolerability of rucaparib in patients with advanced solid tumors. METHODS: Patients with normal hepatic function or moderate hepatic impairment according to the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria were enrolled and received a single oral dose of rucaparib 600 mg. Concentrations of rucaparib and its metabolite M324 in plasma and urine were measured. Pharmacokinetic parameters were compared between hepatic function groups, and safety and tolerability were assessed. RESULTS: Sixteen patients were enrolled (n = 8 per group). Rucaparib maximum concentration (Cmax) was similar, while the area under the concentration-time curve from time 0 to infinity (AUC0-inf) was mildly higher in the moderate hepatic impairment group than in the normal control group (geometric mean ratio, 1.446 [90% CI 0.668-3.131]); similar trends were observed for M324. Eight (50%) patients experienced ≥ 1 treatment-emergent adverse event (TEAE); 2 had normal hepatic function and 6 had moderate hepatic impairment. CONCLUSION: Patients with moderate hepatic impairment showed mildly increased AUC0-inf for rucaparib compared to patients with normal hepatic function. Although more patients with moderate hepatic impairment experienced TEAEs, only 2 TEAEs were considered treatment related. These results suggest no starting dose adjustment is necessary for patients with moderate hepatic impairment; however, close safety monitoring is warranted.

• Klíčová slova
• Hepatic impairment, Pharmacokinetics, Poly(ADP-ribose) polymerase inhibitors, Rucaparib, Safety,
• MeSH
• dospělí MeSH
• indoly farmakokinetika   terapeutické užití   MeSH
• jaterní testy metody   MeSH
• játra účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory farmakoterapie   metabolismus   MeSH
• nemoci jater etiologie   MeSH
• PARP inhibitory farmakokinetika   terapeutické užití   MeSH
• plocha pod křivkou MeSH
• protinádorové látky farmakokinetika   terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• práce podpořená grantem MeSH
• Názvy látek
• indoly MeSH
• PARP inhibitory MeSH
• protinádorové látky MeSH
• rucaparib MeSH Prohlížeč