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

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
› Author Affiliations
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.


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