Pharmacokinetic/pharmacodynamic models for the depletion of Vbeta5.2/5.3 T cells by the monoclonal antibody ATM-027 in patients with multiple sclerosis, as measured by FACS

British Journal of Clinical Pharmacology
Per-Henrik ZingmarkMats O Karlsson

Abstract

(i) To model the effects of the monoclonal antibody ATM-027 on the number of target cells and on the receptor density on the cell surface as measured by Fluorescence Activated Cell Sorter analysis, (ii) to investigate the effects of categorizing a continuous scale, and (iii) to simulate a phase II trial from phase I data in order to evaluate the predictive performance of the model by comparison with the actual trial results. Based on the data from one phase I and one phase II study in multiple sclerosis (MS) patients, models were developed to characterize the pharmacokinetics and pharmacodynamics of the monoclonal antibody ATM-027 and its effects on Vbeta5.2/5.3+ T cells. The pharmacodynamic variables were the number of target T cells and the expression of its receptor. The latter was modelled in both a categorical and continuous way. The modelling was performed with a nonlinear mixed effects approach using the software NONMEM. The joint continuous models were used to simulate the phase II trial from the phase I data. The pharmacokinetics of ATM-027 were characterized by a two-compartment model with a total volume of distribution of 5.9 litres and a terminal half-life of 22.3 days (phase II parameter estimates) in the typical p...Continue Reading

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Citations

Nov 12, 2005·Journal of Pharmacokinetics and Pharmacodynamics·Per-Henrik ZingmarkMats O Karlsson
May 1, 2008·Journal of Pharmacokinetics and Pharmacodynamics·Chantaratsamon DansirikulMats O Karlsson
Sep 24, 2008·Journal of Pharmacokinetics and Pharmacodynamics·Maria C KjellssonMats O Karlsson
Jul 3, 2009·Journal of Pharmacokinetics and Pharmacodynamics·Paul G BaverelMats O Karlsson
Dec 8, 2009·Journal of Pharmacokinetics and Pharmacodynamics·Kayode Ogungbenro, Leon Aarons
Jul 2, 2009·Pharmaceutical Research·Klas J F PeterssonMats O Karlsson
Nov 28, 2012·Clinical Pharmacokinetics·Ines PauleMichel Tod
Aug 4, 2009·The AAPS Journal·Radojka M Savic, Mats O Karlsson
Sep 8, 2010·Clinical Pharmacokinetics·Nathanael L Dirks, Bernd Meibohm
Dec 24, 2017·British Journal of Clinical Pharmacology·Nidal Al-HunitiJianguo Li
Sep 10, 2017·Journal of Pharmacokinetics and Pharmacodynamics·Anne-Gaëlle DosneMats O Karlsson

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