Comparison of Zafirlukast (Accolate®) Absorption After Oral and Colonic Administration in Humans
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Purpose. This study characterized the gastrointestinal (GI) absorptionof 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 distalileum. Serial blood samples were obtained and plasma concentrationswere quantitated by HPLC.
Results. Mean ± SD pharmacokinetic parameters after oral vs. colonicadministration were: AUC∞ of 2076 ± 548 vs. 602 ± 373 ng*h/mL,respectively, and Cmax of 697 ± 314 vs. 194 ± 316 ng/mL, respectively.Mean colon:oral AUC∞ and Cmax were 0.29 and 0.30, respectively.Median tmax values were 2.0 and 1.35 hr after oral and colonicadministration. First-order absorption rate constants (Ka and Kac) wereestimated 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 colonicthan oral administration. Zafirlukast was significantly absorbed in thedistal ileum. This study demonstrated that gamma scintigraphy, digitalradiography, and fluoroscopy can be used to track the movement andconfirm the location of the oroenteric tube in the GI tract.
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