| Author/Editor | Rožman, Samo; Grabnar, Iztok; Novaković, Srdjan; Mrhar, Aleš; Jezeršek Novaković, Barbara | |
| Title | Population pharmacokinetics of rituximab in patients with diffuse large B-cell lymphoma and association with clinical outcome | |
| Type | članek | |
| Vol. and No. | Letnik 83, št. 8 | |
| Publication year | 2017 | |
| Volume | str. 1782-1790 | |
| ISSN | 0306-5251 - British journal of clinical pharmacology | |
| Language | eng | |
| Abstract | Pharmacokinetic (PK) studies suggest that there is a room for improvement in clinical use of rituximab through more individualized treatment. The objective of this study was to characterize rituximab PK in 29 newly diagnosed patients with diffuse large B-cell lymphoma treated with rituximab in combination with cyclophosphamide, doxorubicin, vincristine and methylprednisolone every three weeks. We also evaluated the association of rituximab PK with clinical outcome. METHODS: Rituximab serum levels were determined by enzyme-linked immunosorbent assay and evaluated by a population PK analysis applying non-linear mixed effects modelling. RESULTS: The data were best described by a 2-compartment model comprising linear non-specific clearance of 0.252 (95% CI: 0.227 - 0.279) L/day and time-varying specific clearance of 0.278 (95% CI: 0.181 - 0.390) L/day, corresponding to target-mediated drug disposition of rituximab. Nonspecific clearance was lower in older patients and those with lower body weight. Additionally, volume of the central compartment was higher in males. A clear association of clinical response with rituximab PK has been observed. Rate constant of specific clearance decay was 0.143%day-1 (95% CI: 0.0478 - 0.418) in patients with no disease progression, while in patients with disease progression it was 82.2% lower (95% CI: 33.4 - 95.0). CONCLUSIONS: This finding indicates that time-changes in clearance could serve as a predictive marker of response to rituximab. Our report demonstrates the rationale for studies evaluating higher doses of rituximab in selected patients. | |
| Keywords | rituximab diffuse large B-cell lymphoma pharmacokinetics clinical outcome difuzni velikocelični B-limfom farmakokinetika klinični rezultati kemoterapija |