The Relative Bioavailability and Effects of Food and Acid-Reducing Agents on Filgotinib Tablets in Healthy Subjects

被引:19
作者
Anderson, Kacey [1 ]
Zheng, Hao [1 ]
Kotecha, Mona [1 ]
Cuvin, Jennifer [1 ]
Scott, Bob [1 ]
Sharma, Shringi [2 ]
Qin, Ann Ran-Ran [1 ]
Namour, Florence [3 ]
Xin, Yan [4 ]
机构
[1] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA
[2] Acerta Pharma, San Francisco, CA USA
[3] Galapagos SASU, Romainville, France
[4] Horizon Pharma, Brisbane, CA USA
来源
CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT | 2019年 / 8卷 / 05期
关键词
bioavailability; drug interactions; famotidine; filgotinib; food effects; omeprazole; SELECTIVE JAK1 INHIBITOR; ACTIVE RHEUMATOID-ARTHRITIS; PHARMACOKINETICS; GLPG0634; PHARMACODYNAMICS; KINASES; PH;
D O I
10.1002/cpdd.659
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Filgotinib is a potent, selective Janus kinase-1 inhibitor being developed to treat chronic inflammatory diseases. This phase 1 study in healthy subjects evaluated the relative bioavailability of filgotinib maleate tablets versus the reference tablet (filgotinib hydrochloride) and effects of food and acid-reducing agents (ARAs) on the pharmacokinetics of filgotinib and its major metabolite. Noncompartmental pharmacokinetic parameters of filgotinib and its major metabolite were compared between the 2 tablets at 100- and 200-mg doses and with or without food or ARAs. Filgotinib maleate tablets resulted in equivalent plasma exposures (area under concentration-time curve to infinity [AUC(infinity)] and maximum concentration [C-max]) of filgotinib and its metabolite as the reference tablet (90%CIs of geometric least-squares mean ratios were within the prespecified no-effect boundary of 70% to 143%). Food intake had no effect on filgotinib AUC(infinity), but a high-fat meal reduced C-max by 20%. Coadministration of filgotinib with omeprazole or famotidine had no effect on filgotinib AUC(infinity), but omeprazole decreased C-max by 27%. Neither food nor ARAs affected metabolite exposure. Single-dose filgotinib 100 or 200 mg was well tolerated. This study supports evaluation of filgotinib maleate tablets, administered without regard to food or ARAs, in future clinical studies.
引用
收藏
页码:585 / 594
页数:10
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