Pneumologie 2018; 72(S 01): S46
DOI: 10.1055/s-0037-1619239
Sektion 7 – Klinische Pneumologie
Posterbegehung – Titel: Interstitielle und granulomatöse Lungenerkrankungen II
Georg Thieme Verlag KG Stuttgart · New York

Pharmacokinetics (PK) of nintedanib with add-on pirfenidone in patients with idiopathic pulmonary fibrosis (IPF): results from INJOURNEY

Authors

  • M Kreuter

    1   Center for Interstitial and Rare Lung Diseases, Pneumology, Thoraxklinik, University of Heidelberg; Member of the German Center for Lung Research

  • WA Wuyts

    2   Department of Respiratory Medicine, University Hospitals Leuven

  • JC Grutters

    3   Ild Center of Excellence, Department of Pulmonology, St. Antonius Hospital, and Division of Heart & Lungs, University Medical Center Utrecht

  • L Richeldi

    4   Catholic University of the Sacred Heart, Rome

  • CJ Ryerson

    5   University of British Columbia, Vancouver

  • D Valeyre

    6   Assistance Publique-Hôpitaux de Paris; Avicenne Hospital University, Bobigny

  • S Wiebe

    7   Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach

  • W Stansen

    8   Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein

  • M Quaresma

    9   Center for Interstitial and Rare Lung Diseases, Pneumology, Thoraxklinik, University of Heidelberg; Member of the German Center for Lung Research; Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein

  • S Stowasser

    8   Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein

  • C Vancheri

    10   Department of Clinical and Experimental Medicine, University of Catania
Further Information

Publication History

Publication Date:
21 February 2018 (online)

Also available at
 

Introduction:

In a small phase II trial in Japanese patients with IPF, there was a trend towards lower nintedanib exposure when nintedanib 150 mg bid was added to pirfenidone than when given alone.

Aim:

To explore the PK of nintedanib with add-on pirfenidone.

Methods:

After a 4 – 5 week run-in with nintedanib 150 mg bid, patients with IPF were randomised to open-label nintedanib 150 mg bid with add-on pirfenidone or nintedanib 150 mg bid alone for 12 weeks. In the combination group, patients received pirfenidone 267 mg tid from randomisation to week 1, 534 mg tid from week 1 to week 2, 801 mg tid from week 2. Pre-dose plasma trough concentrations were measured at baseline (for nintedanib) and at weeks 2 and 4 (for nintedanib and pirfenidone).

Results:

Pre-dose pirfenidone gMean (gCV%) concentrations were 1120 (122) and 1220 (91) ng/mL at weeks 2 and 4, respectively. Pre-dose plasma trough concentrations of nintedanib were similar at each time point, irrespective of whether nintedanib 150 mg bid was administered alone or with add-on pirfenidone 534 mg or 801 mg tid (table). Moderate to high variability was observed in both groups.

Nintedanib

150 mg bid alone

Nintedanib 150 mg bid with

add-on pirfenidone

534 mg or 801 mg tid* †

N

gMean (gCV%)

N

gMean (gCV%)

Pre-dose concentration

of nintedanib (ng/mL)

Baseline*

46

7.08 (56.0)

46

7.65 (72.5)

Week 2

41

7.25 (52.7)

35

8.17 (69.8)

Week 4

44

5.92 (73.5)

30

7.13 (63.9)

*Nintedanib 150 mg bid alone at baseline. †Pirfenidone dose titration: 267 mg tid from randomisation to week 1, 534 mg tid from week 1 to week 2. 801 mg tid from week 2.

gCV, geometric coefficient of variation; gMean, geometric mean.

Conclusion:

In patients with IPF, nintedanib plasma trough concentrations were similar when nintedanib was administered alone or with add-on pirfenidone; however, data from a dedicated drug-drug interaction study are needed to draw robust conclusions.