The effect of severe hepatic impairment on the pharmacokinetics and haematological response of C.E.R.A.

ABSTRACTAim: To examine the effect of severe hepatic impairment (HI) on the pharmacokinetics (PK) and pharmacodynamics (PD) of the continuous erythropoietin receptor activator, C.E.R.A.Methods: A non-randomised, multicentre, single-dose, open-label study in patients with HI (n = 12) and healthy subjects (n = 12). After 2 weeks of screening, participants received a single intravenous dose of C.E.R.A. (200 µg), and were then followed for ≈8 weeks. The area under the concentration–time curve (AUC) from drug administration to last measurable concentration (AUClast), and maximum C.E.R.A. concentration (Cmax) were calculated to assess PK. The baseline-corrected area under the effect curve over 22 days (AUEcorr) for reticulocyte count was the primary PD parameter.Results: The PK profile was similar in patients and healthy subjects (AUClast: 6678 vs 6985 ng*h/mL; Cmax: 63 vs 75 ng/mL) C.E.R.A. produced a sustained erythropoietic response in bothgroups, with increases in reticulocyte counts peaking 7–9 days post-d...