Comparison of zafirlukast (Accolate (R)) absorption after oral and colonicadministration in humans

Purpose. This study characterized the gastrointestinal (GI) absorption of z afirlukast 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 fashi on. Two additional subjects were dosed into the distal ileum. Serial blood samples were obtained and plasma concentrations were quantitated by HPLC. Results. Mean rt SD pharmacokinetic parameters after oral vs. colonic admin istration were: AUC(infinity) of 2076 +/- 548 vs. 602 +/- 373 ng*h/mL, resp ectively, and C-max of 697 +/- 314 vs. 194 +/- 316 ng/mL, respectively. Mea n colon:oral AUC(infinity) and C-max were 0.29 and 0.30, respectively. Medi an t(max) values were 2.0 and 1.35 hr after oral and colonic administration . First-order absorption rate constants (K-a and K-ac) were estimated from a two-compartment model with first-order elimination. K-ac:K-a was <0.5 in 4 of the 5 subjects dosed in the colon. Conclusions. Zafirlukast was absorbed at multiple sites in the GI tract. Th e rate and extent of zafirlukast absorption was less after colonic than ora l administration. Zafirlukast was significantly absorbed in the distal ileu m. This study demonstrated that gamma scintigraphy, digital radiography, an d fluoroscopy can be used to track the movement and confirm the location of the oroenteric tube in the GI tract.