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

John M. Kovarik, Mark D. Pescovitz, Hans W. Sollinger, Bruce Kaplan, Christophe Legendre, Kaija Salmela, Benita K. Book, Christophe Gerbeau, Daniele Girault, Kenneth Somberg

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Pharmacokinetic sampling was performed in two multicenter trials in which basiliximab (anti-CD25 monoclonal antibody) was administered with triple immunosuppression consisting of cyclosporine microemulsion, corticosteroids, and either azathioprine or mycophenolate mofetil. Blood samples were collected over 12 wk post-transplant from 31 azathioprine-treated and 66 mycophenolate mofetil-treated patients. Empirical Bayes estimates of each patient's basiliximab disposition parameters were derived and the duration of CD25 saturation was estimated as the time over which serum concentrations exceeded 0.2 μg/mL as confirmed by flow cytometry measurements. Basiliximab clearance was 29 ± 14 mL/h when coadministered with azathioprine and 18 ± 8 mL/h with mycophenolate mofetil. Both were significantly lower compared with a clearance of 37 ± 15 mL/h from a previous study of basiliximab with dual therapy (p<0.001). As a consequence of the lower clearance of basiliximab, the durations of CD25 saturation were prolonged in the presence of azathioprine (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 single patient among 57 who were screened developed anti-idiotype antibodies to basiliximab. The average duration of CD25 saturation was prolonged by 39 and 64% in the presence of azathioprine and mycophenolate mofetil, respectively. This graded effect was also observed for basiliximab clearance and may be due in part to a differentially reduced humoral response to basiliximab. Nonetheless, the range of CD25 saturation durations and basiliximab clearances did not extend outside the range when basiliximab was used with dual therapy in the absence of these agents. Hence, no dosing adjustment is deemed necessary when basiliximab is used in triple immunosuppressive therapy including either azathioprine or mycophenolate mofetil.

Original languageEnglish (US)
Pages (from-to)123-130
Number of pages8
JournalClinical Transplantation
Volume15
Issue number2
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Antibodies
  • Azathioprine
  • Basiliximab
  • Immune response
  • Mycophenolate mofetil

ASJC Scopus subject areas

  • Transplantation

Fingerprint

Dive into the research topics of 'Differential influence of azathioprine and mycophenolate mofetil on the disposition of basiliximab in renal transplant patients'. Together they form a unique fingerprint.

Cite this