title: Lack of effect of casopitant on the pharmacokinetics of docetaxel in patients with cancer.
abstract: OBJECTIVE
  The neurokinin-1 receptor antagonist, casopitant, is a weak-to-moderate inhibitor of cytochrome P450 isoenzyme 3A4 (CYP3A) and has the potential to inhibit the metabolism of CYP3A substrates such as docetaxel.
  
  
  METHODS
  Fourteen cancer patients were enrolled in this phase 1, open-label, randomized, two-period crossover study. Intravenous (i.v.) docetaxel was coadministered with oral ondansetron and dexamethasone with (Regimen B) or without (Regimen A) 150 mg single-dose oral casopitant.
  
  
  RESULTS
  The geometric least-squares mean Regimen B: Regimen A ratios (90% confidence interval) for docetaxel maximum plasma concentration and area under the concentration-time curve from time 0 extrapolated to infinity were 0.97 (0.83, 1.12) and 1.06 (0.94, 1.19), respectively. Coadministration of casopitant and docetaxel was well tolerated, with adverse event profiles and absolute neutrophil count nadirs similar for both treatments.
  
  
  CONCLUSIONS
  C(max) and AUC of docetaxel were similar when given as monotherapy or when given in combination with casopitant. Likewise, absolute neutrophil count nadirs were similar for docetaxel alone or docetaxel with casopitant.
authors.affiliation: Dartmouth Medical School and The Norris Cotton Cancer Center, Lebanon, NH, USA.
authors.forename: Uday B
authors.initials: UB
authors.lastname: Dandamudi
authors.forename: Laurel M
authors.initials: LM
authors.lastname: Adams
authors.forename: Brendan
authors.initials: B
authors.lastname: Johnson
authors.forename: John
authors.initials: J
authors.lastname: Bauman
authors.forename: Shannon
authors.initials: S
authors.lastname: Morris
authors.forename: Sharon
authors.initials: S
authors.lastname: Murray
authors.forename: R Timothy
authors.initials: RT
authors.lastname: Webb
authors.forename: Elaina
authors.initials: E
authors.lastname: Gartner
authors.forename: Raymond
authors.initials: R
authors.lastname: Hohl
authors.forename: Lionel D
authors.initials: LD
authors.lastname: Lewis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000932:Antiemetics / Q000009:adverse effects / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D003907:Dexamethasone / Q000494:pharmacology; D000077143:Docetaxel; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D064729:Neurokinin-1 Receptor Antagonists; D009504:Neutrophils / Q000378:metabolism; D017294:Ondansetron / Q000494:pharmacology; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology*; D010880:Piperidines / Q000009:adverse effects / Q000494:pharmacology*; D043823:Taxoids / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014508:Urea
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D003907:Dexamethasone; D000077143:Docetaxel; D004791:Enzyme Inhibitors; D064729:Neurokinin-1 Receptor Antagonists; D017294:Ondansetron; D010879:Piperazines; D010880:Piperidines; D043823:Taxoids; C531951:casopitant; D014508:Urea; C510163:CYP3A4 protein, human