Brigatinib pharmacokinetics in patients with chronic hepatic impairment

被引:0
|
作者
Michael J. Hanley
David Kerstein
Meera Tugnait
Narayana Narasimhan
Thomas C. Marbury
Karthik Venkatakrishnan
Neeraj Gupta
机构
[1] Takeda Development Center Americas,
[2] Inc.,undefined
[3] Millennium Pharmaceuticals,undefined
[4] Inc.,undefined
[5] a wholly owned subsidiary of Takeda Pharmaceutical Company Limited,undefined
[6] Theseus Pharmaceuticals,undefined
[7] Cerevel Therapeutics,undefined
[8] Orlando Clinical Research Center,undefined
[9] EMD Serono Research and Development Institute,undefined
[10] Inc.,undefined
来源
Investigational New Drugs | 2023年 / 41卷
关键词
Brigatinib; Anaplastic lymphoma kinase; Tyrosine kinase inhibitor; Non-small cell lung cancer; Pharmacokinetics; Hepatic impairment;
D O I
暂无
中图分类号
学科分类号
摘要
Brigatinib is an anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive non-small cell lung cancer. This open-label, parallel-group study investigated the effect of chronic hepatic impairment on the pharmacokinetics (PK) of brigatinib to inform dosing recommendations for these patients. Participants with hepatic impairment classified according to Child-Pugh categories of mild (A), moderate (B), or severe (C) and matched-healthy participants with normal hepatic function received a single oral dose of 90-mg brigatinib. Plasma samples were collected for the determination of brigatinib plasma protein binding and estimation of plasma PK parameters. Twenty-seven participants were enrolled (Child-Pugh A–C, n = 6 each; matched-healthy participants, n = 9). The mean fraction of free plasma brigatinib was comparable for the Child-Pugh A (11.1%), Child-Pugh B (10.8%), and healthy participant groups (8.5%); free brigatinib was higher in the Child-Pugh C group (23.1%). There were no clinically meaningful effects of mild or moderate hepatic impairment on unbound systemic exposures (area under the plasma concentration-time curve [AUC]) of brigatinib (geometric least-squares mean ratios [90% CI] of 89.32% [69.79%–114.31%] and 99.55% [77.78%–127.41%], respectively). In the severe hepatic impairment group, brigatinib unbound AUC was approximately 37% higher (geometric least-squares mean ratio [90% CI] of 137.41% [107.37%–175.86%]) compared with healthy participants with normal hepatic function. Brigatinib was well tolerated in healthy participants and in participants with hepatic impairment. No dose adjustment is required for patients with mild or moderate hepatic impairment. The brigatinib dose should be reduced by approximately 40% for patients with severe hepatic impairment.
引用
收藏
页码:402 / 410
页数:8
相关论文
共 50 条
  • [1] Brigatinib pharmacokinetics in patients with chronic hepatic impairment
    Hanley, Michael J.
    Kerstein, David
    Tugnait, Meera
    Narasimhan, Narayana
    Marbury, Thomas C.
    Venkatakrishnan, Karthik
    Gupta, Neeraj
    [J]. INVESTIGATIONAL NEW DRUGS, 2023, 41 (03) : 402 - 410
  • [2] Effect of severe renal impairment on the pharmacokinetics of brigatinib
    Neeraj Gupta
    Michael J. Hanley
    David Kerstein
    Meera Tugnait
    Narayana Narasimhan
    Thomas C. Marbury
    Karthik Venkatakrishnan
    [J]. Investigational New Drugs, 2021, 39 : 1306 - 1314
  • [3] Effect of severe renal impairment on the pharmacokinetics of brigatinib
    Gupta, Neeraj
    Hanley, Michael J.
    Kerstein, David
    Tugnait, Meera
    Narasimhan, Narayana
    Marbury, Thomas C.
    Venkatakrishnan, Karthik
    [J]. INVESTIGATIONAL NEW DRUGS, 2021, 39 (05) : 1306 - 1314
  • [4] Pharmacokinetics of Antidepressants in Patients with Hepatic Impairment
    Massimo Carlo Mauri
    Alessio Fiorentini
    Silvia Paletta
    Alfredo Carlo Altamura
    [J]. Clinical Pharmacokinetics, 2014, 53 : 1069 - 1081
  • [5] Pharmacokinetics of etoricoxib in patients with hepatic impairment
    Agrawal, NGB
    Rose, MJ
    Matthews, CZ
    Woolf, EJ
    Porras, AG
    Geer, LA
    Larson, PJ
    Cote, J
    Dilzer, SC
    Lasseter, KC
    Alam, I
    Petty, KJ
    Gottesdiener, KM
    [J]. JOURNAL OF CLINICAL PHARMACOLOGY, 2003, 43 (10): : 1136 - 1148
  • [6] Pharmacokinetics of Antidepressants in Patients with Hepatic Impairment
    Mauri, Massimo Carlo
    Fiorentini, Alessio
    Paletta, Silvia
    Altamura, Alfredo Carlo
    [J]. CLINICAL PHARMACOKINETICS, 2014, 53 (12) : 1069 - 1081
  • [7] The pharmacokinetics of escitalopram in patients with hepatic impairment
    Areberg, J
    Christophersen, JS
    Poulsen, MN
    Larsen, F
    Molz, KH
    [J]. AAPS JOURNAL, 2006, 8 (01): : E14 - E19
  • [8] The pharmacokinetics of levamisole in patients with hepatic impairment
    Reiss, WG
    Burstein, AH
    Lee, PID
    PescoKoplowitz, LRC
    Ouyang, P
    Woestenborghs, R
    Kremer, A
    Young, D
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 1997, 61 (02) : PI73 - PI73
  • [9] The pharmacokinetics of escitalopram in patients with hepatic impairment
    Johan Areberg
    Jacob Strøyer Christophersen
    Mette Nøhr Poulsen
    Frank Larsen
    Karl-Heinz Molz
    [J]. The AAPS Journal, 8
  • [10] PHARMACOKINETICS OF OXAPROZIN IN PATIENTS WITH HEPATIC IMPAIRMENT
    LASSETER, KC
    CHIANG, ST
    ROGERS, SL
    WALKER, BR
    [J]. CLINICAL RESEARCH, 1985, 33 (02): : A284 - A284