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Effect of GLPG1205, a GPR84 Modulator, on CYP2C9, CYP2C19, and CYP1A2 Enzymes: In Vitro and Phase 1 Studies
Author(s) -
Desrivot Julie,
Van Kaem Tim,
Allamassey Lisa,
Helmer Eric
Publication year - 2021
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.956
Subject(s) - cyp1a2 , cyp2c19 , pharmacology , medicine , pharmacokinetics , placebo , tolerability , metabolite , cyp2b6 , cyp3a4 , cyp2c9 , crossover study , cytochrome p450 , metabolism , adverse effect , alternative medicine , pathology
GLPG1205 is a novel agent being investigated for the treatment of idiopathic pulmonary fibrosis. GLPG1205 may be concomitantly administered with pirfenidone in future clinical development; therefore, the potential for GLPG1205 to interact with enzymes involved in the metabolism of pirfenidone (cytochrome P450 [CYP] 1A2, CYP2C9, 2C19) was evaluated. In vitro experiments indicated weak inhibition of CYP1A2 and moderate but reversible inhibition of CYP2C9 and CYP2C19 by GLPG1205. A phase 1 randomized, double‐blind crossover study in 14 healthy males (NCT02623296) evaluated the effect of GLPG1205 100 mg or placebo (once daily for 12 days) on the single‐dose pharmacokinetics of a cocktail of CYP1A2, CYP2C9, and CYP2C19 substrates (coadministered on day 13). GLPG1205 had no effect on the exposure of CYP2C9 and CYP1A2 substrates or metabolites; however, a trend toward increased omeprazole (CYP2C19 substrate) exposure was observed. Although considered not clinically relevant, GLPG1205 increased the elimination rate of 5‐hydroxyomeprazole (CYP2C19 metabolite) 1.16‐fold versus placebo. GLPG1205 had no effect on the elimination of all other substrates or metabolites. GLPG1205 had a favorable safety and tolerability profile. In conclusion, GLPG1205 100 mg once daily does not interact with CYP2C9, CYP2C19, or CYP1A2 to a clinically relevant extent and may be administered concomitantly with drugs metabolized by these enzymes.