title: Pharmacokinetics and delivery of the anti-influenza prodrug oseltamivir to the small intestine and colon using site-specific delivery capsules.
abstract: This study investigated the site-specific absorption of oseltamivir using targeted delivery and gamma scintigraphy. On four separate occasions, nine healthy male subjects each received a single 150 mg of oseltamivir administered via the Enterion capsule to the stomach, proximal small bowel, distal small bowel and the ascending colon. Pharmacokinetic parameters of oseltamivir and its carboxylate metabolite show that absorption was similar in the proximal and distal small bowel compared to stomach delivery, but reduced from the ascending colon, demonstrating that absorption-rate limited disposition occurred only for the ascending colon. The metabolite-to-parent ratios were minimally reduced. The results support the feasibility of modified-release formulation development whilst confirming the high and consistent oral bioavailability of oseltamivir.
authors.affiliation: Department of Clinical Pharmacology, Hoffmann-La Roche Inc., Nutley, NJ, USA. charles.oo@aventis.com
authors.forename: Charles
authors.initials: C
authors.lastname: Oo
authors.forename: Paul
authors.initials: P
authors.lastname: Snell
authors.forename: Joanne
authors.initials: J
authors.lastname: Barrett
authors.forename: Albert
authors.initials: A
authors.lastname: Dorr
authors.forename: Baolian
authors.initials: B
authors.lastname: Liu
authors.forename: Ian
authors.initials: I
authors.lastname: Wilding
mesh_terms: D000081:Acetamides / Q000493:pharmacokinetics*; D000328:Adult; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D002214:Capsules; D003106:Colon / Q000378:metabolism*; D018592:Cross-Over Studies; D016503:Drug Delivery Systems; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy*; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053139:Oseltamivir; D011355:Prodrugs / Q000493:pharmacokinetics*
chemical_list: D000081:Acetamides; D000998:Antiviral Agents; D002214:Capsules; D011355:Prodrugs; D053139:Oseltamivir