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@article{1676540, author = {Rolfo, C. and Isambert, N. and Italiano, A. and Molife, L. R. and Schellens, J. H. and Blay, J. Y. and Decaens, T. and Kristeleit, R. and Rosmorduc, O. and Demlová, Regina and Lee, M. A. and Ravaud, A. and Kopeckova, Katerina and Learoyd, M. and Bannister, W. and Locker, G. and de VosandGeelen, J.}, article_location = {HOBOKEN}, article_number = {9}, doi = {http://dx.doi.org/10.1111/bcp.14283}, keywords = {advanced solid tumours; hepatic impairment; liver; olaparib; pharmacokinetics; poly(ADP-ribose) polymerase; safety}, language = {eng}, issn = {0306-5251}, journal = {BRITISH JOURNAL OF CLINICAL PHARMACOLOGY}, title = {Pharmacokinetics and safety of olaparib in patients with advanced solid tumours and mild or moderate hepatic impairment}, url = {https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bcp.14283}, volume = {86}, year = {2020} }
TY - JOUR ID - 1676540 AU - Rolfo, C. - Isambert, N. - Italiano, A. - Molife, L. R. - Schellens, J. H. - Blay, J. Y. - Decaens, T. - Kristeleit, R. - Rosmorduc, O. - Demlová, Regina - Lee, M. A. - Ravaud, A. - Kopeckova, Katerina - Learoyd, M. - Bannister, W. - Locker, G. - de Vos-Geelen, J. PY - 2020 TI - Pharmacokinetics and safety of olaparib in patients with advanced solid tumours and mild or moderate hepatic impairment JF - BRITISH JOURNAL OF CLINICAL PHARMACOLOGY VL - 86 IS - 9 SP - 1807-1818 EP - 1807-1818 PB - WILEY SN - 03065251 KW - advanced solid tumours KW - hepatic impairment KW - liver KW - olaparib KW - pharmacokinetics KW - poly(ADP-ribose) polymerase KW - safety UR - https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bcp.14283 L2 - https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bcp.14283 N2 - Aims Olaparib, a potent oral poly(ADP-ribose) polymerase inhibitor, is partially hepatically cleared. We investigated the pharmacokinetics (PK) and safety of olaparib in patients with mild or moderate hepatic impairment to provide dosing recommendations. Methods This Phase I open-label study assessed the PK, safety and tolerability of single doses of olaparib 300-mg tablets in patients with advanced solid tumours. Patients had normal hepatic function (NHF), or mild (MiHI; Child-Pugh class A) or moderate (MoHI; Child-Pugh class B) hepatic impairment. Blood was collected for PK assessments for 96 hours. Patients could continue taking olaparib 300 mg twice daily for long-term safety assessment. Results Thirty-one patients received >= 1 dose of olaparib and 30 were included in the PK assessment. Patients with MiHI had an area under the curve geometric least-squares mean (GLSmean) ratio of 1.15 (90% confidence interval 0.72, 1.83) and a GLSmean maximum plasma concentration ratio of 1.13 (0.82, 1.56)vsthose with NHF. In patients with MoHI, GLSmean ratio for area under the curve was 1.08 (0.66, 1.74) and for maximum plasma concentration was 0.87 (0.63, 1.22)vsthose with NHF. For patients with mild or moderate hepatic impairment, no new safety signals were detected. Conclusion Patients with MiHI or MoHI had no clinically significant changes in exposure to olaparib compared with patients with NHF. The safety profile of olaparib did not differ from a clinically relevant extent between cohorts. No olaparib tablet or capsule dose reductions are required for patients with MiHI or MoHI. ER -
ROLFO, C., N. ISAMBERT, A. ITALIANO, L. R. MOLIFE, J. H. SCHELLENS, J. Y. BLAY, T. DECAENS, R. KRISTELEIT, O. ROSMORDUC, Regina DEMLOVÁ, M. A. LEE, A. RAVAUD, Katerina KOPECKOVA, M. LEAROYD, W. BANNISTER, G. LOCKER and J. DE VOS-GEELEN. Pharmacokinetics and safety of olaparib in patients with advanced solid tumours and mild or moderate hepatic impairment. \textit{BRITISH JOURNAL OF CLINICAL PHARMACOLOGY}. HOBOKEN: WILEY, 2020, vol.~86, No~9, p.~1807-1818. ISSN~0306-5251. Available from: https://dx.doi.org/10.1111/bcp.14283.
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