The pharmacokinetics of brensocatib in participants with renal impairment following a single oral administration

肾功能 医学 药代动力学 耐受性 泌尿科 不利影响 口服 内科学
作者
Sam Au Yeung,Daniel S. Stein,Thomas Marbury,Helen Usansky
出处
期刊:British Journal of Clinical Pharmacology [Wiley]
标识
DOI:10.1111/bcp.16344
摘要

Aim Brensocatib is an oral, selective, competitive and reversible dipeptidyl peptidase 1 inhibitor in development for the treatment of bronchiectasis. This study evaluated the pharmacokinetics (PKs), safety and tolerability of brensocatib in participants with varying degrees of renal impairment and normal renal function. Methods In this phase 1, multicentre, open‐label study, 28 participants with mild, moderate or severe renal impairment (estimated glomerular filtration rate [eGFR] 60 to <90, 30 to <60 and 15 to <30 mL/min/1.73 m 2 , respectively) or normal renal function (≥90 mL/min/1.73 m 2 ) received a single oral 25‐mg dose of brensocatib. Blood samples were collected to measure brensocatib PKs at predetermined time points over the 14‐day study period. PK parameters were derived using noncompartmental methods. Results Demographic and baseline characteristics were similar across groups. There were no significant differences between groups in brensocatib PK parameters. The mean coefficient of variation (CV) of elimination half‐life of brensocatib was 37.0 (15.3), 42.8 (21.7), 36.3 (22.9) and 39.1 (17.8) h for mild, moderate, severe and normal renal function groups, respectively. Single‐dose brensocatib was quickly absorbed; all groups had a median time to maximum observed plasma concentration of 1 h. Regression model analyses indicated no significant relationships between selected brensocatib PK parameters and eGFR. No treatment‐emergent adverse events were reported during the study. Conclusion Single‐dose brensocatib was well tolerated. The study data do not indicate a significant effect of renal impairment on brensocatib elimination and systemic exposure, suggesting that dose adjustment of brensocatib is not necessary in participants with renal impairment. Clinical Trial Registration Number NCT05673603.
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