Abstract
Zamicastat is a reversible dopamine β-hydroxylase inhibitor that modulate sympathetic nervous system by reducing noradrenaline biosynthesis in peripheral sympathetic nerves. It is currently being developed BIAL - Portela & Cª, S.A. for the treatment of Pulmonary Arterial Hypertension (PAH). As sildenafil may be concomitantly administered with zamicastat in PAH treatment, the potential for drug-drug interactions was investigated.
This was an open-label, three period, fixed sequence study in 20 healthy subjects to assess the effect of single dose (SD) of zamicastat on the steady-state pharmacokinetics (PK) of sildenafil and the effect of sildenafil on the PK of zamicastat under fasting conditions, as follows: first period, SD of zamicastat 400 mg, second period, sildenafil 20mg t.i.d from Day 1 to Day 5 and a SD on Day 6; third period, sildenafil 20 mg t.i.d from Day 1 to Day 5, and on Day 6 a concomitant SD of zamicastat 400 mg and sildenafil 20 mg. 90%-confidence intervals (90%CIs) for the geometric mean ratio (GMR) of Cmax, AUC0-t and AUC0-τ,ss of zamicastat and sildenafil were calculated for the comparison between alone vs. concomitant administration.
The GMR (90% CI) for Cmax and AUC0-t of zamicastat were 101% (85-119%) and 94% (79-111%), respectively. The GMR (90%CI) for Cmax,ss and AUC0-τ,ss of sildenafil were 100% (84-118%) and 98% (89-107%), respectively. Co-administration of single-dose of zamicastat and sildenafil under steady-state did not significantly affect the peak and total exposure of either drugs. Zamicastat was safe and well tolerated when administered alone and concomitantly with sildenafil.
Footnotes
Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 1458.
This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.
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 2020