Clinical Pharmacokinetic Characteristics of Cebranopadol, a Novel First-in-Class AnalgesicReportar como inadecuado

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Clinical Pharmacokinetics

pp 1–20

First Online: 16 June 2017DOI: 10.1007-s40262-017-0545-1

Cite this article as: Kleideiter, E., Piana, C., Wang, S. et al. Clin Pharmacokinet 2017. doi:10.1007-s40262-017-0545-1


Background and ObjectivesCebranopadol is a novel first-in-class analgesic acting as a nociceptin-orphanin FQ peptide and opioid peptide receptor agonist with central analgesic activity. It is currently in clinical development for the treatment of chronic pain conditions. This trial focuses on the clinical pharmacokinetic PK properties of cebranopadol after oral single- and multiple-dose administration.

MethodsThe basic PK properties of cebranopadol were assessed by means of noncompartmental methods in six phase I clinical trials in healthy subjects and patients. A population PK analysis included two further phase I and six phase II clinical trials.

ResultsAfter oral administration of the immediate-release IR formulation, cebranopadol is characterized by a late time to reach maximum plasma concentration Cmax 4–6 h, a long half-value duration HVD 14–15 h, and a terminal phase half-life in the range of 62–96 h. After multiple once-daily dosing in patients, an operational half-life the dosing interval resulting in an accumulation factor AF of 2 of 24 h was found to be the relevant factor to describe the multiple-dose PKs of cebranopadol. The time to reach steady state was approximately 2 weeks, the AF was approximately 2, and peak-trough fluctuation PTF was low 70–80%. Dose proportionality at steady state was shown for a broad dose range of cebranopadol 200–1600 µg. A two-compartment disposition model with two lagged transition compartments and a first-order elimination process best describes cebranopadol data in healthy subjects and patients after single- and multiple-dose administration.

ConclusionsCebranopadol formulated as an IR product can be used as a once-daily formulation; it reaches Cmax after only 4–6 h, and has a long HVD and a low PTF. Therefore, from a PK perspective, cebranopadol is an attractive treatment option for patients with chronic pain.

Autor: Elke Kleideiter - Chiara Piana - Shaonan Wang - Robert Nemeth - Michael Gautrois


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