Population pharmacokinetic analysis of letermovir in adult hematopoietic cell transplant recipients.

Abstract

We analyzed previously reported oral letermovir plasma concentration measurements from 40 allogeneic hematopoietic cell transplant (HCT) recipients using model-based pharmacometrics analysis. This analysis highlighted that the industry-sponsored phase III study model significantly over-predicted observed letermovir concentrations. Covariates associated with increased oral clearance (CL/F), possibly contributing to this observation, included: higher weight, younger age, and early use after HCT. The clinical significance and mechanistic explanation of relatively lower real-world exposure remains to be elucidated.