title: Aprepitant pharmacokinetics and assessing the impact of aprepitant on cyclophosphamide metabolism in cancer patients undergoing hematopoietic stem cell transplantation.
abstract: Aprepitant, a neurokinin antagonist, is an effective antiemetic agent in chemotherapy for delayed nausea and vomiting. The study objective was to evaluate the pharmacokinetics of aprepitant and concurrent cyclophosphamide (CY), often a component of hematopoietic stem cell transplant (HSCT) conditioning regimen, in cancer patients undergoing HSCT. Forty subjects were randomized to either aprepitant or placebo in addition to standard antiemetics. Aprepitant or placebo was started 1 hour before the first chemotherapy or radiation dose for HSCT conditioning and administered daily until 4 days after infusion of the hematopoietic cell graft (for a total of 10-12 days). Serial blood samples were collected for aprepitant and CY plus 2 important CY metabolites. The results indicate that aprepitant is well absorbed and does not auto-induce its metabolism. No significant drug interaction was observed with CY or its metabolites. A significant portion of the patients had subtherapeutic aprepitant concentrations; however, chemotherapy-induced nausea and vomiting were effectively managed. No dosage adjustment was necessary, and administration of aprepitant in HSCT at the prescribed dosage of 125 mg orally on day 1 and 80 mg orally on each consecutive day through day +4 after HSCT was well tolerated with no significant changes in CY pharmacokinetic parameters.
authors.affiliation: Department of Pharmacy Practice, Oregon State University and Oregon Health & Science University, College of Pharmacy, Portland, OR 97239-4501, USA. cheralag@ohsu.edu
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Bubalo
authors.forename: Ganesh
authors.initials: G
authors.lastname: Cherala
authors.forename: Jeannine S
authors.initials: JS
authors.lastname: McCune
authors.forename: Myrna Y
authors.initials: MY
authors.lastname: Munar
authors.forename: Sunny
authors.initials: S
authors.lastname: Tse
authors.forename: Richard
authors.initials: R
authors.lastname: Maziarz
mesh_terms: D000328:Adult; D000932:Antiemetics / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077608:Aprepitant; D003520:Cyclophosphamide / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control; D009369:Neoplasms / Q000628:therapy; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control; D055815:Young Adult
chemical_list: D000932:Antiemetics; D018906:Antineoplastic Agents, Alkylating; D009025:Morpholines; D000077608:Aprepitant; D003520:Cyclophosphamide