J Clin Pharmacol. 2022 Sep 4. doi: 10.1002/jcph.2148. Online ahead of print.
ABSTRACT
Enarodustat (JTZ-951) is a hypoxia-inducible factor prolyl hydroxylase inhibitor that has been approved and marketed in Japan for anemic patients with chronic kidney disease (CKD). The pharmacometric approach was applied to assess the relationship between plasma concentrations of enarodustat and hemoglobin (Hb) levels, and to provide information regarding the optimal use of enarodustat in clinical practice by simulations based on the pharmacokinetic and pharmacodynamic (PK/PD) model that was developed. The PK/PD data of enarodusat obtained from Phase 2 and Phase 3 studies in Japanese CKD patients were well described by the models: a 1-comportment model with first-order absorption and elimination for PK, and a semi-mechanistic model based on transit compartment model for PD. Although several factors were identified as statistically significant covariates on the PK/PD of enarodustat, model-based simulations showed that none of them had clinically relevant impacts on the treatment effect (i.e., Hb levels) of enarodustat. Hence, enarodustat treatment provides the stable Hb control with the initial dose (hemodialysis dependent CKD: 4 mg/day, non-dialysis dependent CKD: 2 mg/day) and maintenance dose (1 to 8 mg/day) to the patients with varied demographic characteristics. This article is protected by copyright. All rights reserved.
PMID:36057843 | DOI:10.1002/jcph.2148
