Population Pharmacokinetics of Liposomal Irinotecan in Patients With Cancer

被引：47

作者：

Adiwijaya, B. S. ^{[1
]}

Kim, J. ^{[1
]}

Lang, I. ^{[2
]}

Csoszi, T. ^{[3
]}

Cubillo, A. ^{[4
]}

Chen, J-S ^{[5
]}

Wong, M. ^{[6
]}

Park, J. O. ^{[7
]}

Kim, J. S. ^{[8
]}

Rau, K. M. ^{[9
]}

Melichar, B. ^{[10
]}

Gallego, J. B. ^{[11
]}

Fitzgerald, J. ^{[1
]}

Belanger, B. ^{[1
]}

Molnar, I. ^{[1
]}

Ma, W. W. ^{[12
]}

机构：

[1] Merrimack Pharmaceut Inc, Cambridge, MA 02139 USA

[2] Natl Inst Oncol, Budapest, Hungary

[3] JNSZ Megyei Hetenyi Geza Korhaz Rendelointezet, Szolnok, Hungary

[4] Ctr Integral Oncol Clara Campal, Madrid, Spain

[5] Chang Gung Mem Hosp, Linkou Branch, Taoyuan, Taiwan

[6] Westmead Hosp, Westmead, NSW, Australia

[7] Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Seoul, South Korea

[8] Korea Univ, Guro Hosp, Seoul, South Korea

[9] Chang Gung Mem Hosp, Kaohsiung Branch, Kaohsiung, Taiwan

[10] Univ Palackeho, Onkol Klin, Lekarska Fak, Fak Nemocnice, Olomouc, Czech Republic

[11] Hosp Gen Elche, Elche, Spain

[12] Mayo Clin, Rochester, MN USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2017年 / 102卷 / 06期

关键词：

INDUCED LIVER-INJURY; HEART-FAILURE; MECHANISTIC MODEL; CELL-DEATH; HEPATOTOXICITY; DYSFUNCTION; TOXICITY; PREVALENCE; BIOMARKERS; DILISYM(R);

D O I：

10.1002/cpt.720

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Nanoliposomal irinotecan (nal-IRI) is a liposomal formulation of irinotecan with a longer half-life (t(1/2)), higher plasma total irinotecan (tIRI), and lower SN-38 maximum concentration (C-max) compared with nonliposomal irinotecan. Population pharmacokinetic (PK) analysis of nal-IRI was performed for tIRI and total SN-38 (tSN38) using patient samples from six studies. PK-safety association was evaluated for neutropenia and diarrhea in 353 patients. PK-efficacy association was evaluated from a phase III study in pancreatic cancer NAPOLI1. Efficacy was associated with longer duration of unencapsulated SN-38 (uSN38) above a threshold and higher C-avg of tIRI, tSN38, and uSN38. Neutropenia was associated with uSN38 C-max and diarrhea with tIRI C-max. Baseline predictive factors were race, body surface area, and bilirubin. Analysis identified PK factors associated with efficacy, safety, and predictive baseline factors. The results support the benefit of nal-IRI dose of 70mg/m(2) (free-base; equivalent to 80mg/m(2) salt base) Q2W over 100mg/m(2) Q3W.

引用

页码：997 / 1005

页数：9

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