Article date: August 2017
By: Bertrand Lioger, Soujanya Ratna Edupuganti, Denis Mulleman, Christophe Passot, Céline Desvignes, Théodora Bejan‐Angoulvant, Gilles Thibault, Valérie Gouilleux‐Gruart, Julien Mélet, Gilles Paintaud, David Ternant in Volume 83, Issue 8, pages 1773-1781
Aims
Rituximab is a monoclonal antibody directed against CD20, which is approved in rheumatoid arthritis (RA). This study aimed at assessing the influence of CD19+ cell counts as target‐antigen amount, and of immunoglobulin G (IgG) serum concentrations on rituximab pharmacokinetics in RA patients.
Methods
In a cohort of 64 RA patients who had received repetitive courses of rituximab, the influence of CD19+ cell count, IgG serum concentration, body surface area, sex and disease activity score in 28 joints on rituximab pharmacokinetic parameters was assessed using a population pharmacokinetic analysis.
Results
A two‐compartment model, with first‐order distribution and elimination best described the data. The volume of distribution of central compartment and clearance of rituximab were estimated at 4.7 l and 0.56 l day–1, respectively. Distribution and elimination half‐lives were 0.9 days and 17.3 days, respectively. As expected, the central volume of distribution increased with body surface area (P = 0.012) and was higher in male than in female (P = 0.004). We found that the elimination rate constant (k10) increased with CD19+ count (P = 0.00022) and IgG concentration (P = 7.4 × 10−8), and that k10 decreased with time (P = 0.00015), partly explained by a change in target‐antigen amount.
Conclusions
The association between CD19+ count and k10 may be explained by target‐mediated drug disposition, while the association between IgG serum concentration and k10 may be explained by a saturation of the neonatal Fc receptor at high IgG concentrations, resulting in decreased recycling of rituximab.
DOI: 10.1111/bcp.13270
View this article