Erdafitinib's effect on serum phosphate justifies its pharmacodynamically guided dosing in patients with cancer.

A population pharmacokinetic (PK)-pharmacodynamic (PD) model was developed using data from 345 patients with cancer. The population PK-PD model evaluated the effect of erdafitinib total and free plasma concentrations on serum phosphate concentrations after once-daily oral continuous (0.5-12 mg) and intermittent (10-12 mg for 7 days on/7 days off) dosing, and investigated the potential covariates affecting erdafitinib-related changes in serum phosphate levels.

Effect of Ponesimod Exposure on Total Lymphocyte Dynamics in Patients with Multiple Sclerosis.

Objective: The aim of this study was to characterize the relationship between ponesimod plasma concentrations and the temporal evolution of lymphocyte counts in multiple sclerosis (MS) patients.

Methods: Population pharmacokinetic (PK) and PK/pharmacodynamic (PD) models were developed using data from phase I, II, and III trials, and the impact of clinically relevant covariates on PK and PD parameters was assessed. Simulations were conducted to evaluate the maximal lymphocyte count reduction after ponesimod treatment, and the time required for total lymphocyte counts to return to normal values after treatment interruption.

Target engagement and cellular fate of otelixizumab: a repeat dose escalation study of an anti-CD3ε mAb in new-onset type 1 diabetes mellitus patients.

Aims: This paper describes the pharmacological findings from a study where otelixizumab, an anti-CD3ɛ mAb, was dosed in new onset Type 1 diabetes mellitus (NOT1DM) patients. This is the first time that the full dose-response of an anti-CD3ɛ mAb has been investigated in the clinic. The data have been validated using a previously developed pharmacokinetic/pharmacodynamic (PK/PD) model of otelixizumab to simulate the interplay between drug administration, CD3ɛ target engagement and downmodulation.