Pharmacokinetics of rituximab associated with CHOP chemotherapy in B‐cell non‐Hodgkin lymphoma

Abstract

The pharmacokinetics of rituximab administered alone at a dose of 375 mg/m(2) once a week have been widely studied but few data are available for the administration of rituximab in combination with other agents. We carried out a pilot pharmacokinetic study in 10 patients with B-cell non-Hodgkin lymphoma treated with rituximab associated with chemotherapy on a three-weekly basis. Patients received four courses of rituximab (375 mg/m(2)) associated with CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) at 21-day intervals. Blood samples were collected from each patient at selected times throughout the treatment period and analysed using a validated enzyme-linked immunosorbent assay. The NONMEM software was used to obtain population and post hoc estimates of rituximab pharmacokinetic parameters and to study possible time-dependent variation during treatment. Pharmacokinetic parameters obtained from 10 patients were similar to those described for studies in the absence of chemotherapy. We did not observe any intra-subject variation in pharmacokinetic parameters over the treatment period. Our results suggest that rituximab pharmacokinetics is not affected by combination with CHOP chemotherapy. Nevertheless, the substantial intersubject variability observed in this small sample size highlights the need for further study of the determinants of rituximab pharmacokinetic variability.

The role of sex and weight on rituximab clearance and serum elimination half-life in elderly patients with DLBCL

“…The pharmacokinetics of rituximab was appropriately described by a 2-compartmental model in our study, confirming previously published studies (Table 6), even though different subroutines for population analysis were used. 11,17 Whereas subroutines other than ADVAN TRAN have been suggested as the best-fitting routine for NONMEM, adequate calculation of t 1/2␤ can only be obtained by Vd ss calculated with the ADVAN3 TRANS3 subroutine in NONMEM (as demonstrated in this study).…”

“…Population-pharmacokinetic information about rituximab is available from only a few studies performed in different patient populations: in patients with rheumatoid arthritis, 17 in 8 patients with mostly indolent non-Hodgkin lymphoma, 14 and 10 patients with mostly DLBCL. 11 To the best of our knowledge, this is the first study on rituximab pharmacokinetics for a dose-dense 2-week R-CHOP-14 schedule in patients with aggressive CD20 ϩ B-cell lymphoma. A comparison of our study with the pharmacokinetic results of previous studies is shown in Table 6.…”

“…25,26 Our results are in agreement with another study in which actual concentrations of the first treatment cycle were used to simulate concentrations of later cycles. 11 In that study, the simulated values were compared with the measured values and they did not differ. It was concluded that the pharmacokinetic behavior of rituximab was not altered despite the treatment-induced tumor mass reduction.…”

“…Compared with a population pharmacokinetic analysis described previously, 11 our investigation yielded a structural 2-compartment model as the best-fitting model based on the first-order conditional expectation and the NONMEM subroutines ADVAN3 TRANS3. Based on this subroutine, the corresponding pharmacokinetic parameters Cl, central volume (V 1 ), intercompartmental clearance (Q), and Vd ss were calculated.…”

Comparative assessment of pharmacokinetics, and pharmacodynamics between RTXM83™, a rituximab biosimilar, and rituximab in diffuse large B-cell lymphoma patients: a population PK model approach

“…The analyses and simulations were performed using NON-MEM Version 7.3.0 software [9], supplemented with the PsN toolkit version 4.4.8 [10], and were further processed using R Version 3.2.0 [11]. NONMEM data sets were prepared using SAS 9.4 (SAS Institute Inc., Cary, NC, USA).…”