A drug-drug interaction study of ibrutinib with moderate/strong CYP3A inhibitors in patients with B-cell malignancies

被引：32

作者：

de Jong, Jan ^{[1
]}

Hellemans, Peter ^{[2
]}

De Wilde, Severijn ^{[2
]}

Patricia, Daniel ^{[3
]}

Masterson, Tara ^{[3
]}

Manikhas, Georgii ^{[4
]}

Myasnikov, Alexander ^{[5
]}

Osmanov, Dzhelil ^{[6
]}

Cordoba, Raul ^{[7
]}

Panizo, Carlos ^{[8
]}

de Zwart, Loeckie ^{[2
]}

Snoeys, Jan ^{[2
]}

Chauhan, Vijay ^{[9
]}

Jiao, James ^{[9
]}

Sukbuntherng, Juthamas ^{[10
]}

Ouellet, Daniele ^{[3
]}

机构：

[1] Janssen Res & Dev LLC, 3210 Merryfield Row, San Diego, CA 92121 USA

[2] Janssen Res & Dev, Beerse, Belgium

[3] Janssen Res & Dev, Spring House, PA USA

[4] St Petersburg City Oncol Hosp, St Petersburg, Russia

[5] Baranov Republican Hosp, Petrozavodsk, Russia

[6] NN Blokhin Russian Acad Med Sci, Moscow, Russia

[7] Univ Hosp Fdn Jimenez Diaz, START Madrid, Hlth Res Inst IIS FJD, Madrid, Spain

[8] Univ Clin Navarra, Pamplona, Spain

[9] Janssen Res & Dev, Raritan, NJ USA

[10] Pharmacyclics LLC, Sunnyvale, CA USA

来源：

LEUKEMIA & LYMPHOMA | 2018年 / 59卷 / 12期

关键词：

Erythromycin; CYP3A; ibrutinib; pharmacokinetics; voriconazole; CHRONIC LYMPHOCYTIC-LEUKEMIA; PHARMACOKINETICS; PCI-32765; THERAPY;

D O I：

10.1080/10428194.2018.1460474

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

This was an open-label, multicenter, phase-1 study to evaluate the drug interaction between steady-state ibrutinib and moderate (erythromycin) and strong (voriconazole) CYP3A inhibitors in patients with B-cell malignancies and to confirm dosing recommendations. During cycle 1, patients received oral ibrutinib 560 mg qd alone (Days 1-4 and 14-18), and ibrutinib 140 mg (Days 5-13; 19-27) plus erythromycin 500 mg tid (Days 5-11) and voriconazole 200 mg bid (Days 19-25). Twenty-six patients (median [range] age: 64.5 [50-88] years) were enrolled. Geometric mean ratio (90% confidence intervals) after co-administration of ibrutinib 140 mg with erythromycin and voriconazole was 74.7 (53.97-103.51) and 143.3 (107.77-190.42), respectively, versus ibrutinib 560 mg alone. The most common (>= 20%) adverse events were diarrhea (27%) and neutropenia (23%). The results demonstrate that ibrutinib 140 mg with voriconazole or erythromycin provides exposure within the clinical range for patients with B-cell malignancies.

引用

页码：2888 / 2895

页数：8

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