In vitro-in vivo correlation of percutaneous absorption: isosorbide dinitrate and morphine hydrochloride.
The potential of an in vitro skin preparation as a model for predicting in vivo percutaneous absorption of drugs was examined. In vitro and in vivo skin permeation data for two model drugs with different lipophilicity, isosorbide dinitrate (ISDN) and morphine hydrochloride (MPH), were compared using pharmacokinetic techniques. In vitro permeation data published previously were analyzed based on a single pathway model, and permeation parameters were obtained. The disposition parameters were estimated from the plasma concentration profiles after i.v. administration. The plasma concentrations after topical application were then simulated using the obtained permeation and disposition parameters, and the values were compared with the corresponding observed ones. Although the simulated plasma concentration curves were not greatly different from those observed, there were some differences in the time course-pattern. Causes for these in vitro-in vivo differences were discussed.
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
T
T
Hatanaka
K
K
Katayama
T
T
Koizumi
K
K
Sugibayashi
Y
Y
Morimoto
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D009020:Morphine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D012869:Skin Absorption
D009020:Morphine; D007548:Isosorbide Dinitrate