Effect of aprepitant on intravenous tacrolimus disposition in reduced intensity hematopoietic stem cell transplantation.
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.
Department of Pharmacy/Karmanos Cancer Hospital, 4100 John R, Detroit, MI 48201-2013, USA. ibrahim@karmanos.org
Rami B
RB
Ibrahim
Muneer H
MH
Abidi
Lois J
LJ
Ayash
Simon M
SM
Cronin
Cheryl
C
Cadotte
Jason
J
Mulawa
Pamela A
PA
Jacobson
Daryn W
DW
Smith
Joseph P
JP
Uberti
David J
DJ
Edwards
D000293:Adolescent; D000328:Adult; D000932:Antiemetics / Q000494:pharmacology* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000627:therapeutic use; D000077608:Aprepitant; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology*; D009181:Mycoses / Q000517:prevention & control; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
D000932:Antiemetics; D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D009025:Morpholines; D000077608:Aprepitant; D015725:Fluconazole; D016559:Tacrolimus