title: The effect of formulation and food consumption on the bioavailability of dovitinib (TKI258) in patients with advanced solid tumors.
abstract: OBJECTIVE
  This 2-arm, phase 1, crossover study compared the relative bioavailability of two dovitinib (TKI258) capsule formulations [anhydrate clinical service form (CSF) and monohydrate final market image (FMI); Arm 1] and determined the effect of food on dovitinib exposure (Arm 2).
  
  
  METHODS
  Patients with advanced solid tumors were enrolled in one of the 2 arms. Arm 1 randomized patients to a single 500-mg dose of either CSF or FMI followed by 7 days of rest and 500 mg of the other formulation. Arm 2 patients received 300 mg of FMI once daily and were randomized to follow one of six meal sequences, each with three prandial conditions: low fat (LF), high fat (HF), or no meal (NM).
  
  
  RESULTS
  Twenty-three and 37 patients were enrolled and 19 and 21 were evaluable in Arms 1 and 2, respectively. In Arm 1, the adjusted geometric means for FMI had small reductions relative to CSF [area under the plasma concentration-time curve (AUClast) decreased by 12%, maximum concentration (C max) decreased by 3%]. In Arm 2, the HF meal versus NM showed a 2% increase in the adjusted geometric mean for AUClast and a 5% decrease for C max. The LF meal versus NM comparison showed 9 and 6% increases for AUClast and C max, respectively. Overall, common adverse events included nausea, vomiting, diarrhea, and fatigue.
  
  
  CONCLUSIONS
  Systemic exposure to dovitinib was similar for the FMI and CSF capsule formulations. Additionally, since prandial conditions did not affect the systemic exposure, dovitinib can be taken with or without food.
authors.affiliation: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Dr, Rm 3360, Salt Lake City, UT, 84112, USA, sunil.sharma@hci.utah.edu.
authors.forename: Sunil
authors.initials: S
authors.lastname: Sharma
authors.forename: Carolyn D
authors.initials: CD
authors.lastname: Britten
authors.forename: Joanne
authors.initials: J
authors.lastname: Mortimer
authors.forename: Swarupa
authors.initials: S
authors.lastname: Kulkarni
authors.forename: Michelle
authors.initials: M
authors.lastname: Quinlan
authors.forename: Angela
authors.initials: A
authors.lastname: Liu
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Scott
authors.forename: Daniel
authors.initials: D
authors.lastname: George
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D002214:Capsules; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000009:adverse effects*; D005260:Female; D005504:Food Analysis / Q000379:methods; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
chemical_list: C500007:4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D002214:Capsules; D004041:Dietary Fats; D015363:Quinolones