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DOI: 10.1055/s-0037-1619239
Pharmacokinetics (PK) of nintedanib with add-on pirfenidone in patients with idiopathic pulmonary fibrosis (IPF): results from INJOURNEY
Publikationsverlauf
Publikationsdatum:
21. Februar 2018 (online)
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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