This Article Full Text (PDF) A correction has been published All Versions of this Article: 1078155208089846v1 14/3/113    most recent References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Ibrahim, R. B Articles by Edwards, D. J Search for Related Content PubMed PubMed Citation Articles by Ibrahim, R. B Articles by Edwards, D. J Social Bookmarking                         What's this?

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

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, ibrahim{at}karmanos.org

Muneer H Abidi, MD

Bone Marrow Transplantation Service, Karmanos Cancer Institute, 4100 John R, Detroit, MI 48201-2013, USA, Medicine, School of Medicine, Wayne State University

Lois J Ayash, MD

Bone Marrow Transplantation Service, Karmanos Cancer Institute, 4100 John R, Detroit, MI 48201-2013, USA, Medicine, School of Medicine, Wayne State University

Simon M Cronin, MS PharmD BCOP

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

Cheryl Cadotte, PharmD

Harper University Hospital, Detroit Medical Center, 3990 John R, Detroit, MI 48201, USA

Jason Mulawa, PharmD

Eugene Applebaum College of Pharmacy and Allied Health Professions/Wayne State University, 259 Mack, Detroit, MI, 48201, USA

Pamela A Jacobson, PharmD

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

Daryn W Smith, MS

Biostatistics Core, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201-2013, USA

Joseph P Uberti, MD PhD

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

David J Edwards, PharmD

Chair, Pharmacy Practice, Eugene Applebaum College of Pharmacy and Allied Health Professions, Wayne State University, 259 Mack, Detroit, MI, 48201, USA

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. J Oncol Pharm Practice (2008) 14: 113—121.

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

This version was published on September 1, 2008

Journal of Oncology Pharmacy Practice, Vol. 14, No. 3, 113-121 (2008)
DOI: 10.1177/1078155208089846


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?