The influence of green tea extract on nintedanib’s bioavailability in patients with pulmonary fibrosis

Abstract

Nintedanib is an oral small-molecule kinase inhibitor and first-line treatment for idiopathic pulmonary fibrosis. Nintedanib is a substrate of the drug efflux transporter ABCB1. Green tea flavonoids --especially epigallocatechin gallate (EGCG)-- are potent ABCB1 modulators. We investigated if concomitant administration of green tea extract (GTE) could result in a clinically relevant herb-drug interaction.Patients were randomized between A-B and B-A, with A being nintedanib alone and B nintedanib with GTE. Both periods lasted 7 days, in which nintedanib was administered twice daily directly after a meal. In period B, patients additionally received capsules with GTE (500 mg BID, >60% EGCG). Pharmacokinetic sampling for 12 h was performed at day 7 of each period. Primary endpoint was change in geometric mean for the area under the curve (AUC0–12 h). A linear mixed model was used to analyse AUCs and maximal concentration (Cmax).In 26 included patients, the nintedanib AUC0–12 h was 21% lower (95% CI −29% to −12%; P T wild type variant. No differences in toxicities were observed.Exposure to nintedanib decreased with 21% when administered 60 min after GTC for only 7 days. This is a statistically significant interaction which could potentially impair treatment efficacy. Before patients and physicians should definitely be warned to avoid this combination, prospective clinical validation of an exposure-response relationship is necessary.

Keywords

• Nintedanib
• Pharmacokinetics
• Green tea
• Flavonoids
• Interaction
• Pulmonary fibrosis