Site-specific drug delivery in the dog using flexible fiberoptic endoscopy.
The development of a nonsurgical repeatable method of site-specific delivery to the gastrointestinal tract in the canine is described. Studies to characterize and validate this method were performed utilizing propranolol and etodolac due to their well-known pharmacokinetic properties. Using a catheter placed through the auxiliary port of a flexible fiberoptic endoscope, liquid dosage formulations were consistently delivered to the canine stomach, duodenum, ileum, and colon. It was shown that differences in site-specific delivery could be demonstrated with this model. Propranolol tended to have the highest exposure following dosing to the ileum as compared to other sites. The anesthetic regimen used to perform endoscopy affected certain pharmacokinetic parameters of the compounds being tested including decreasing the intrinsic clearance of propranolol. However, since decreased intrinsic clearance should similarly affect AUCo regardless of the site of delivery, this does not preclude site-specific comparisons to be made. Further, no evidence has been reported for the effect of anesthesia on one GI segment but not another. Thus for other compounds, assuming there are either no anesthetic effects on intestinal pharmacokinetic parameters (absorption, intestinal metabolism, etc.) or that they are consistent and uniform throughout the intestinal tract, this model allows comparisons of the exposure following delivery to differing intestinal sites.
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Drug Safety and Metabolism, Wyeth-Ayerst Research, 641 Ridge Road, Chazy, New York 12921, USA.
Smith
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Enever
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D000818:Animals; D019540:Area Under Curve; D004285:Dogs; D016503:Drug Delivery Systems; D020776:Endoscopes, Gastrointestinal; D017308:Etodolac / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005336:Fiber Optic Technology; D008297:Male; D011433:Propranolol / Q000008:administration & dosage* / Q000493:pharmacokinetics
D017308:Etodolac; D011433:Propranolol