Differential influence of azathioprine and mycophenolate mofetil on the disposition of basiliximab in renal transplant patients

Pharmacokinetic sampling was performed in two multicenter trials in which b asiliximab (anti-CD25 monoclonal antibody) was administered with triple imm unosuppression consisting of cyclosporine microemulsion, corticosteroids, a nd either azathioprine or mycophenolate mofetil. Blood samples were collect ed over 12 wk post-transplant from 31 azathioprine-treated and 66 mycopheno late mofetil-treated patients. Empirical Bayes estimates of each patient's basiliximab disposition parameters were derived and the duration of CD25 sa turation was estimated as the time over which serum concentrations exceeded 0.2 mug/mL as confirmed by flow cytometry measurements. Basiliximab cleara nce was 29 +/- 14 mL/h when coadministered with azathioprine and 18 +/- 8 m L/h with mycophenolate mofetil. Both were significantly lower compared with a clearance of 37 +/- 15 mL/h from a previous study of basiliximab with du al therapy (p < 0.001). As a consequence of the lower clearance of basilixi mab, the durations of CD25 saturation were prolonged in the presence of aza thioprine (50 +/- 20 d; range, 13-84) and mycophenolate mofetil (59 +/- 17 d; range, 28-94) compared with dual therapy (36 +/- 14 d; range. 12-91). A total of 27 acute rejection episodes occurred during the first 6 months: in the two studies. Durations of CD25 saturation were not different in these patients compared with those who remained rejection-free in each study. A s ingle patient among 57 who were screened developed anti-idiotype antibodies to basiliximab. The average duration of CD25 saturation was prolonged by 3 9 and 64% in the presence of azathioprine and mycophenolate mofetil, respec tively. This graded effect was also observed for basiliximab clearance and may be due in part to a differentially reduced humoral response to basilixi mab. Nonetheless, the range of CD25 saturation durations and basiliximab cl earances did not extend outside the range when basiliximab was used with du al therapy in the absence of these agents. Hence, no dosing adjustment is d eemed necessary when basiliximab is used in triple immunosuppressive therap y including either azathioprine or mycophenolate mofetil.