Abstract
Zamicastat is a reversible dopamine β-hydroxylase inhibitor that modulates sympathetic activity by reducing norepinephrine biosynthesis in peripheral sympathetic nerves. Zamicastat was granted Orphan Drug Designation by Food and Drug Administration (FDA) for the treatment of Pulmonary Arterial Hypertension (PAH). As zamicastat may be concomitantly administered with furosemide in PAH patients, the potential for a drug-drug interaction was investigated.
Study BIA-51058-111 was an open-label, single dose (SD), fasted, 3-period, fixed sequence study in 44 healthy subjects to assess the effect of zamicastat on furosemide pharmacokinetics (PK), and the effect of furosemide on zamicastat PK. During periods 1 and 2, subjects received zamicastat 400 mg SD and furosemide 40 mg SD, respectively, whilst during period 3 subjects received 40 mg SD furosemide concomitant with 400 mg SD of zamicastat. The 90%-confidence intervals (90%CIs) for the geometric mean ratio (GMR) of PK parameters (Cmax, AUC0-t and AUC 0-inf) of both drugs were calculated for the comparison between concomitant administration vs. alone.
The GMR (90% CI) for Cmax, AUC0-t and AUC0-inf of zamicastat were 98% (86-111%), 104% (96-113%) and 101% (94-108%), respectively, whilst for furosemide were 58% (50-66%), 74% (68-81%) and 75% (64-87%), respectively. Zamicastat decreased mean Cmax, AUC0-t and AUC0-inf of furosemide by 42%, 26% and 25%, respectively. Furosemide had no effect on Cmax and AUC of zamicastat.
Zamicastat was safe and well tolerated when administered alone or with furosemide. The dose of furosemide may need to be adjusted to the individual clinical response, if these drugs are concomitantly administered.
Footnotes
Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA1930.
This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2021