Effect of aprepitant on intravenous tacrolimus disposition in reduced intensity hematopoietic stem cell transplantation

Rami B. Ibrahim, Muneer H. Abidi, Lois J. Ayash, Simon M. Cronin, Cheryl Cadotte, Jason Mulawa, Pamela A. Jacobson, Daryn W. Smith, Joseph P. Uberti, David J. Edwards

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Aprepitant (AP) is a known inhibitor of cytochrome P450 3A4 which may affect tacrolimus metabolism. We retrospectively examined the effect of oral AP on intravenous tacrolimus concentrations in 26 patients undergoing reduced intensity transplantation from 09/2005 to 09/2006. Oral AP 125 mg daily was administered on transplant day +1 and 80 mg on days +2 and +3. Intravenous tacrolimus was administered as a 0.03 mg/kg/ day continuous infusion on day -6 through day +1 (pre-AP), during-AP (days +2 to +7), and post-AP starting on day +8. Tacrolimus doses were adjusted to achieve concentrations of 5-20 ng/mL. Dose-corrected tacrolimus concentrations (ng/mL/mg per dose) in the pre-AP, during-AP, and post-AP time periods were: 8.12 (95% CI: 7.3-9.1), 11.63 (95% CI: 9.63-13.63), and 11.42 (95% CI: 8.12-14.7), respectively (P < 0.01 between pre-AP and during-AP, P < 0.01 between during-AP and post-AP, P = 0.01 between pre-AP and post-AP time periods). Although statistically significant, the observed rise was not clinically significant between during-AP and post-AP time periods. Previous work has shown that AP is not expected to exert an inhibitory effect within 48 h of AP discontinuation. Collectively, these data suggest that AP effect on tacrolimus metabolism is of minor clinical significance. A controlled trial is needed to confirm these findings.

Original languageEnglish (US)
Pages (from-to)113-121
Number of pages9
JournalJournal of Oncology Pharmacy Practice
Volume14
Issue number3
DOIs
StatePublished - Jan 1 2008

Keywords

  • Aprepitant
  • Cytochrome CYP3A4
  • Inhibition
  • Interaction
  • Tacrolimus

Fingerprint Dive into the research topics of 'Effect of aprepitant on intravenous tacrolimus disposition in reduced intensity hematopoietic stem cell transplantation'. Together they form a unique fingerprint.

Cite this