Pharmacokinetics and safety of olaparib in patients with
advanced solid tumours and mild or moderate hepatic impairment

J 2020

Pharmacokinetics and safety of olaparib in patients with advanced solid tumours and mild or moderate hepatic impairment

ROLFO, C., N. ISAMBERT, A. ITALIANO, L. R. MOLIFE, J. H. SCHELLENS et. al.

Basic information

Original name

Pharmacokinetics and safety of olaparib in patients with advanced solid tumours and mild or moderate hepatic impairment

Authors

ROLFO, C. (840 United States of America, guarantor), N. ISAMBERT (250 France), A. ITALIANO (250 France), L. R. MOLIFE (826 United Kingdom of Great Britain and Northern Ireland), J. H. SCHELLENS (528 Netherlands), J. Y. BLAY (528 Netherlands), T. DECAENS (250 France), R. KRISTELEIT (528 Netherlands), O. ROSMORDUC (250 France), Regina DEMLOVÁ (203 Czech Republic, belonging to the institution), M. A. LEE (410 Republic of Korea), A. RAVAUD (250 France), Katerina KOPECKOVA (203 Czech Republic), M. LEAROYD (826 United Kingdom of Great Britain and Northern Ireland), W. BANNISTER (826 United Kingdom of Great Britain and Northern Ireland), G. LOCKER (826 United Kingdom of Great Britain and Northern Ireland) and J. DE VOS-GEELEN (528 Netherlands)

Edition

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, HOBOKEN, WILEY, 2020, 0306-5251

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.335

RIV identification code

RIV/00216224:14110/20:00116307

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1111/bcp.14283

UT WoS

000557473800001

Keywords in English

advanced solid tumours; hepatic impairment; liver; olaparib; pharmacokinetics; poly(ADP-ribose) polymerase; safety

Abstract

V originále

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.

Citovat

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. 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.

@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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