Comparison of zafirlukast (Accolate) absorption after oral and colonic administration in humans.
OBJECTIVE
This study characterized the gastrointestinal (GI) absorption of zafirlukast after oral and colonic administration in humans.


METHODS
Five healthy subjects received zafirlukast solution (40 mg) orally and via an oroenteric tube into the colon in a randomized, crossover fashion. Two additional subjects were dosed into the distal ileum. Serial blood samples were obtained and plasma concentrations were quantitated by HPLC.


RESULTS
Mean +/- SD pharmacokinetic parameters after oral vs. colonic administration were: AUC infinity of 2076 +/- 548 vs. 602 +/- 373 ng x h/mL, respectively, and Cmax of 697 +/- 314 vs. 194 +/- 316 ng/mL, respectively. Mean colon:oral AUCalpha and Cmax were 0.29 and 0.30, respectively. Median tmax values were 2.0 and 1.35 hr after oral and colonic administration. First-order absorption rate constants (Ka and Kac) were estimated from a two-compartment model with first-order elimination. Kac:Ka was <0.5 in 4 of the 5 subjects dosed in the colon.


CONCLUSIONS
Zafirlukast was absorbed at multiple sites in the GI tract. The rate and extent of zafirlukast absorption was less after colonic than oral administration. Zafirlukast was significantly absorbed in the distal ileum. This study demonstrated that gamma scintigraphy, digital radiography, and fluoroscopy can be used to track the movement and confirm the location of the oroenteric tube in the GI tract.
Fischer
J D
JD
School of Pharmacy, University of North Carolina, Chapel Hill 27599, USA.
Song
M H
MH
Suttle
A B
AB
Heizer
W D
WD
Burns
C B
CB
Vargo
D L
DL
Brouwer
K L
KL
D000284:Administration, Oral; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002404:Catheterization; D003106:Colon / Q000378:metabolism*; D018592:Cross-Over Studies; D015902:Gamma Cameras; D006801:Humans; D007082:Ileum / Q000378:metabolism; D007211:Indoles; D007408:Intestinal Absorption; D007441:Intubation, Gastrointestinal; D008297:Male; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*
D018927:Anti-Asthmatic Agents; D007211:Indoles; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds; C062735:zafirlukast