In vivo approach to determine the route of optimal drug absorption in rats.
The purpose of this paper is to describe the methodology to evaluate the optimal route of absorption in rats, avoiding the first pass effect of the liver (nasal, buccal and transdermal). These routes were investigated for a new benzamide, for which an absorption profile close to the intramuscular route is desired. Nasal route was investigated on anaesthetized rats by perfusion at a feeble flow rate of a recirculated solution through a tube from a reservoir, to the posterior part of the nasal cavity. Buccal absorption was evaluated by means of an original perfusion model adapted from the nasal recirculation model. Transdermal absorption was realized using a very simple "reservoir" system developed in our laboratory, which permits the application of the drug solution directly onto the skin. Action of some vehicles on nasal and transdermal drug absorption was studied. Absorption parameters, e.g. rate input and extent of drug input versus time were calculated by numerical deconvolution using the intramuscular route as reference. Results were evaluated and the most adequate route presenting absorption characteristics closest to those researched was further studied for application in man. In the present example, the drug was better absorbed when administered by nasal route.
Lhote
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O
Departement de Biopharmacie, Laboratoires Delagrange, France.
Decoodt
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A
Moulin
A
A
Dufour
A
A
D000042:Absorption; D000279:Administration, Cutaneous; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D002610:Cheek; D005079:Excipients; D007273:Injections, Intramuscular; D008297:Male; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D010599:Pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption
D005079:Excipients; D004364:Pharmaceutical Preparations