Back to Journals » Drug Design, Development and Therapy » Volume 12

Pharmacokinetics of single- and multiple-dose roflumilast: an open-label, three-way crossover study in healthy Chinese volunteers

Authors Huang J, Fu CX, Yang XY, Cui C, Yang S, Kuang Y, Guo CX, Hu P, Pei Q, Yang GP

Received 2 July 2018

Accepted for publication 22 October 2018

Published 26 November 2018 Volume 2018:12 Pages 4047—4057


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Sukesh Voruganti

Jie Huang,1,2,* Cheng-xiao Fu,1,2,* Xiao-yan Yang,1,2 Chan Cui,1,2 Shuang Yang,1,2 Yun Kuang,1,2 Cheng-xian Guo,1,2 Pei Hu,3 Qi Pei,2,4 Guo-ping Yang1,2

1Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China; 2Center for Clinical Drug Evaluation, Central South University, Changsha, Hunan 410013, People’s Republic of China; 3Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing 100032, People’s Republic of China; 4Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China

*These authors contributed equally to this work

Purpose: To determine the pharmacokinetic properties of the common tablet of roflumilast administered in single and multiple oral doses in Chinese subjects.
Subjects and methods: Both the single- and multiple-dose studies included 12 adults (6 males and 6 females). In this single-center, open-label study, single doses of 0.25, 0.375, and 0.5 mg were administered using a randomized, three-way crossover design, and then, the 0.375 mg dose was continued for 11 days once daily. The pharmacokinetic parameters for roflumilast and roflumilast N-oxide were determined and the safety evaluation included adverse events assessed by monitoring, physical examination, vital sign tests, and clinical laboratory tests.
Results: After every single dose, the time to the maximum concentration (Cmax) of roflumilast (Tmax) was 0.25–2.0 hours; thereafter, the concentration declined, with a mean half-life (t1/2) of 19.7–20.9 hours over the range of 0.25–0.50 mg. As for roflumilast N-oxide, the mean t1/2 was 23.2–26.2 hours. The area under curve from the beginning to 24 hours (AUC0–24 h), the AUC until infinity (AUCinf), and the Cmax of roflumilast and roflumilast N-oxide increased in a dose-proportional manner. After multiple doses, the accumulation index (Rac) on the 11th day of the steady state was ~1.63 for roflumilast and 3.20 for roflumilast N-oxide. No significant sex differences were observed in the pharmacokinetic parameters of roflumilast and roflumilast N-oxide. In addition, there were no serious adverse events across the trial.
Conclusion: Roflumilast was safe and well-tolerated in healthy volunteers, and a linear increase in its Cmax and AUC values was observed at doses ranging from 0.25 to 0.50 mg.

pharmacokinetics, roflumilast, roflumilast N-oxide, healthy volunteer, phosphodiesterase 4 inhibitor

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]