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.

Základní údaje

Originální název

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

Autoři

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.340

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/20:00116307

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

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

Štítky

14110516, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 29. 10. 2020 13:26, Mgr. Tereza Miškechová

Anotace

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 a 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, roč. 86, č. 9, s. 1807-1818. ISSN 0306-5251. Dostupné z: https://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 = {https://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 a 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, roč.~86, č.~9, s.~1807-1818. ISSN~0306-5251. Dostupné z: https://doi.org/10.1111/bcp.14283.

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