Effect of lopinavir/ritonavir on the pharmacokinetics of selexipag an oral prostacyclin receptor agonist and its active metabolite in healthy subjects.


First published in British Journal of Clinical Pharmacology on 2015 Oct.
Br J Clin Pharmacol. 2015 Oct;80(4):670-7. doi: 10.1111/bcp.12650. Epub 2015 Jun 12

Authors: Kaufmann P, Niglis S, Bruderer S, Segrestaa J, Äänismaa P, Halabi A, Dingemanse J.



This study investigated the effect of a fixed dose combination of lopinavir/ritonavir on the pharmacokinetics (pharmacokinetics) of selexipag and its active metabolite ACT-333679.


This was an open label, randomized, single centre, two way, crossover study. Twenty healthy male subjects were treated with a single dose of 400 µg selexipag alone and in combination with multiple doses of lopinavir/ritonavir (400/100 mg) twice daily.


The results showed that lopinavir/ritonavir approximately doubled the exposure to selexipag. The area under the plasma concentration-time curve from time zero to infinity (AUC(0,∞) and the maximum plasma concentration (Cmax) of selexipag were 2.2- and 2.1-fold higher, respectively, than under selexipag alone, with a 90% confidence interval (CI) of the geometric mean ratio (GMR) of 1.9, 2.7 and 1.7, 2.6, respectively. For ACT-333679, the clinically more relevant component of selexipag, systemic exposure was increased by 8% (GMR of AUC(0,∞) 1.1, 90% CI 0.9, 1.3), when lopinavir/ritonavir was co-administered with selexipag. The most frequently reported adverse event (AE) was headache. A single dose of selexipag, administered either alone or together with multiple doses of lopinavir/ritonavir, was safe and well tolerated.


Lopinavir/ritonavir does not affect the pharmacokinetics parameters of selexipag and ACT-333679 to a clinically relevant extent. Therefore, adaptation of the selexipag dose is not required when co-administered with inhibitors of the organic anion-transporting polypeptide (OATP) 1B1/ 1B3, P-glycoprotein (P-gp) and/or CYP3A4.

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