title: The NK₁ receptor antagonist aprepitant does not alter the pharmacokinetics of high-dose melphalan chemotherapy in patients with multiple myeloma.
abstract: OBJECTIVE
  The objective of this investigation was to assess the effect of aprepitant on the pharmacokinetics of high-dose melphalan used as conditioning therapy before blood stem cell transplantation in multiple myeloma.
  
  
  METHODS
  Aprepitant (125 mg) or placebo was administered 1 h before melphalan therapy (1 h infusion of 100 mg m⁻²). Eleven plasma samples were obtained over 8 h and melphalan was quantified using an LC/MS/MS method. Standard pharmacokinetic parameters were calculated and nonparametric testing was applied to assess the differences between aprepitant and placebo treatment.
  
  
  RESULTS
  Twenty patients received placebo and 10 patients aprepitant treatment. There were no differences observed for C(max) at the end of melphalan infusion (placebo 3431 ± 608 ng ml⁻¹ vs. aprepitant 3269 ± 660 ng ml⁻¹). In addition, AUC and terminal elimination half-life were not changed by aprepitant. Total clearance of melphalan was 304 ± 58 ml min⁻¹ m⁻² (placebo) which was not influenced by aprepitant (288 ± 78 ml min⁻¹ m⁻²).
  
  
  CONCLUSIONS
  The administration of the NK₁ receptor antagonist aprepitant 1 h before a high-dose chemotherapy does not influence the exposure and the elimination of melphalan. Therefore, oral administration of 125 mg aprepitant 1 h before melphalan infusion does not alter the disposition of intravenously administered melphalan.
authors.affiliation: Department of Internal Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Germany. gerlinde.egerer@med.uni-heidelberg.de
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Egerer
authors.forename: Kathrin
authors.initials: K
authors.lastname: Eisenlohr
authors.forename: Martina
authors.initials: M
authors.lastname: Gronkowski
authors.forename: Juergen
authors.initials: J
authors.lastname: Burhenne
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Riedel
authors.forename: Gerd
authors.initials: G
authors.lastname: Mikus
mesh_terms: D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000097:blood*; D000077608:Aprepitant; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000097:blood*; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000097:blood* / Q000188:drug therapy; D064729:Neurokinin-1 Receptor Antagonists; D011446:Prospective Studies; D019172:Transplantation Conditioning / Q000379:methods
chemical_list: D000932:Antiemetics; D018906:Antineoplastic Agents, Alkylating; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D000077608:Aprepitant; D008558:Melphalan