Population pharmacokinetics of trastuzumab in patients With HER2+ metastatic breast cancer

Abstract

This population pharmacokinetic model can predict trastuzumab exposure in the long-term treatment of patients with metastatic breast cancer and provide comparison of alternative dosage regimens via simulation.

Population pharmacokinetics of the humanised monoclonal antibody, HuHMFG1 (AS1402), derived from a phase I study on breast cancer

“…Rarely does a combined linear and non-linear process describe the elimination of antibodies (Kuester et al, 2008). Values of the final parameters were similar to those reported for other antibodies, with regard to CL from the central compartment and Q, V1 and V2 (Kovarik et al, 2001;Bruno et al, 2005;Ng et al, 2006;Dartois et al, 2007;Mould et al, 2007;Kuester et al, 2008;Lu et al, 2008). This indicates that the HuHMFG1 antibody, similar to other therapeutic antibodies, is mainly distributed in the serum.…”

“…In contrast, in cases in which hepatic enzymes have been investigated as covariates in population PK modelling for other antibodies, they were found not to be significantly relevant (Kuester et al, 2008;Lu et al, 2008;Newsome and Ernstoff, 2008). Alanine aminotransferase has been found to be strongly linked to another covariate and then eliminated during the removal step of covariate study for trastuzumab (Bruno et al, 2005), and ALP was found to be significantly linked to the clearance of pertuzumab (Ng et al, 2006). In this study, when only AST was retained during the removal step, ALP and GGT were also found to be linked to the clearance of HuHMFG1 during the first step of covariate study.…”

“…Indeed, a structural two-compartmental model is commonly reported to describe the behaviour of antibodies. In these models, the associated elimination is mainly linear (Kovarik et al, 2001;Bruno et al, 2005;Ng et al, 2006;Dartois et al, 2007) and less frequently non-linear (Mould et al, 1999(Mould et al, , 2007. Rarely does a combined linear and non-linear process describe the elimination of antibodies (Kuester et al, 2008).…”

Application of Quantitative Pharmacology in Development of Therapeutic Monoclonal Antibodies

“…Many of the antibodies in development or currently marketed recognize membraneassociated antigens (28,32,37,(71)(72)(73)(74)(75)(76)(77)(78)(79)(80). Interaction of antibodies with this class of target antigen can greatly impact their PK.…”

Pharmacocinétique des anticorps monoclonaux

“…Chez les souris ayant une réponse transitoire, suivie d'une nouvelle croissance de la masse tumorale, les concentrations d'infliximab ne sont pas modifiées alors que l'élimination du rituximab est accélérée. Il a par ailleurs été montré que le nombre de sites métastati-ques influence la PK du trastuzumab chez les patientes traitées [35]. Pour décrire l'interdépendance entre la PK et la pharmacodynamie, des modèles pharmacocinétiques-pharmacodynamiques (PK-PD) spécifiques doivent être développés [37,38].…”