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

¹ Clinical Pharmacy Specialist (Hematology/Oncology), Department of Pharmacy/Karmanos Cancer Institute, Adjunct-Assistant Professor, Pharmacy Practice, Eugene Applebaum College of Pharmacy and Allied Health Professions, Wayne State University, 4100 John R, Detroit, MI 48201-2013, USA
² Bone Marrow Transplantation Service, Karmanos Cancer Institute, 4100 John R, Detroit, MI 48201-2013, USA, Associate Professor of Medicine, School of Medicine, Wayne State University
³ Clinical Pharmacy Specialist (Hematology/Oncology), Department of Pharmacy/Karmanos Cancer Hospital, Adjunct-Associate Professor/Eugene Applebaum College of Pharmacy and Allied Health Professions/Wayne State University, 4100 John R, Detroit, MI 48201-2013, USA
⁴ Harper University Hospital, Detroit Medical Center, 3990 John R, Detroit, MI 48201, USA
⁵ Eugene Applebaum College of Pharmacy and Allied Health Professions/Wayne State University, 259 Mack, Detroit, MI, 48201, USA
⁶ Associate Professor, Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 308 Harvard Street East, 7–159 Weaver-Densford Hall, Minneapolis, MN 55455, USA
⁷ Biostatistics Core, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201-2013, USA
⁸ Bone Marrow Transplantation program director, Karmanos Cancer Institute, Professor of Medicine, School of Medicine, Wayne State University, 4100 John R, Detroit, MI, 48201-2013, USA
⁹ Chair, Pharmacy Practice, Eugene Applebaum College of Pharmacy and Allied Health Professions, Wayne State University, 259 Mack, Detroit, MI, 48201, USA

^* To whom correspondence should be addressed.

	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.

Key Words: tacrolimus; aprepitant; inhibition; cytochrome CYP3A4; interaction

First published on June 13, 2008, doi:10.1177/1078155208089846

Journal of Oncology Pharmacy Practice 2008;14:113.

A more recent version of this article appeared on September 1, 2008


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