PMID- 15598479
OWN - NLM
STAT- MEDLINE
DCOM- 20050308
LR  - 20181201
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 26
IP  - 10
DP  - 2004 Oct
TI  - Relative bioavailability and safety profile of gefitinib administered as a tablet 
      or as a dispersion preparation via drink or nasogastric tube: results of a 
      randomized, open-label, three-period crossover study in healthy volunteers.
PG  - 1630-6
AB  - BACKGROUND: Many patients with head and neck cancer have difficulty swallowing 
      tablet formulations of medications, and use of dispersion preparations may be 
      advantageous. OBJECTIVE: The aim of the present study was to determine the 
      relative bioavailability and safety profile of a single dose of gefitinib, an 
      orally active inhibitor of epidermal growth factor receptor tyrosine kinase, when 
      administered as a whole 250-mg tablet or as a dispersion preparation via drink or 
      nasogastric tube in healthy male volunteers. METHODS: This was a Phase 1, 
      randomized, open-label, 3-period crossover study. Plasma samples obtained before 
      dosing to 240 hours after dosing were analyzed for gefitinib using reverse-phase 
      high-performance liquid chromatography with tandem mass-spectrometric detection. 
      The pharmacokinetic parameters of interest included AUC, C(max), and the relative 
      bioavailability of the dispersion via drink or nasogastric tube compared with the 
      standard tablet. RESULTS: Eighteen healthy white male volunteers were enrolled. 
      They had a mean age of 43 years (range, 21-59 years), mean body weight of 85.1 kg 
      (range, 60-101 kg), and mean height of 180.3 cm (range, 171-187 cm). The 
      geometric mean AUC was 2219 ng.h/mL for a single 250-mg dose of gefitinib 
      administered as a whole tablet, 2233 ng.h/mL for the dispersion preparation 
      administered by drink, and 2007 ng.h/mL for the dispersion preparation 
      administered by nasogastric tube. The corresponding values for the geometric mean 
      C(max) were 95.2, 96.3, and 89.9 ng/mL. The gefitinib dispersion preparation 
      administered by drink had a mean bioavailability of 103.8% relative to the whole 
      tablet; the dispersion preparation administered by nasogastric tube had a mean 
      bioavailability of 99.1% relative to the whole tablet. For the drink-tablet and 
      nasogastric tube-tablet comparisons, the estimate-of-treatment ratios for the AUC 
      were a respective 1.006 and 0.928; for the C(max), they were 1.012 and 0.964. 
      There appeared to be no clinically significant differences in absorption or 
      elimination between the preparations. Three volunteers experienced adverse events 
      (AEs) that were considered possibly related to gefitinib (pruritus and dry skin), 
      and 6 volunteers experienced procedure-related AEs (cannula-site reaction and 
      rhinorrhea); these AEs were mild or moderate. No serious AEs were recorded, and 
      no AEs led to withdrawal of any volunteer. CONCLUSIONS: Administration of a 
      250-mg dose of gefitinib as a dispersion preparation by drink or nasogastric tube 
      achieved a systemic exposure to gefitinib that was consistent with that achieved 
      when gefitinib was administered as a whole tablet. There was no evidence of 
      tolerability problems associated with the routes of administration studied in 
      these healthy volunteers.
FAU - Cantarini, Mireille V
AU  - Cantarini MV
AD  - AstraZenea, Alderley Park, Macclesfield, Cheshire, SK0 4TG, UK. 
      mireille.cantarini@astrazeneca.com
FAU - McFarquhar, Teresa
AU  - McFarquhar T
FAU - Smith, Robert P
AU  - Smith RP
FAU - Bailey, Chris
AU  - Bailey C
FAU - Marshall, Anna L
AU  - Marshall AL
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Quinazolines)
RN  - 0 (Tablets)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Antineoplastic Agents/*administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Area Under Curve
MH  - Beverages
MH  - Biological Availability
MH  - Cross-Over Studies
MH  - Epidermal Growth Factor/antagonists & inhibitors
MH  - Gefitinib
MH  - Humans
MH  - Intubation, Gastrointestinal
MH  - Male
MH  - Middle Aged
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors
MH  - Quinazolines/*administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Tablets
EDAT- 2004/12/16 09:00
MHDA- 2005/03/09 09:00
CRDT- 2004/12/16 09:00
PHST- 2004/08/25 00:00 [accepted]
PHST- 2004/12/16 09:00 [pubmed]
PHST- 2005/03/09 09:00 [medline]
PHST- 2004/12/16 09:00 [entrez]
AID - S0149-2918(04)80311-4 [pii]
AID - 10.1016/j.clinthera.2004.10.011 [doi]
PST - ppublish
SO  - Clin Ther. 2004 Oct;26(10):1630-6. doi: 10.1016/j.clinthera.2004.10.011.