Transdermal drug pharmacokinetics in man: Interindividual variability and partial prediction


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Abstract

A database of human dermatopharmacokinetic parameters of 12 transdermal patches is established. The effect of system design, application site, and metabolism on pharmacokinetic data is discussed, and interindividual variability of data and its possible sources evaluated. Using multiple regression analysis, two equations based on drugs physicochemical characteristics are suggested for partial prediction of peak plasma concentration (Cmax) after patch application. Patch application presumably decreases variance as rub-off, wash and exfoliation steps are diminished.The results showed that interindividual variation, in terms of coefficient of variation (CV) of Cmax, is inversely correlated with drugs molecular weight and lipophilicity in the range of 200 < MW < 400 and 1.6 < log Koct < 4.3. Multiple regression analysis of Cmax against physichochemical parameters demonstrated the prominent contribution of hydrogen bonding acceptability of the molecules on their maximal plasma concentration after patch administration.The findings suggest that the serum concentration profile for transdermal therapeutic systems (TTS) is a net result of the system performance, drug absorption and elimination. Thus, the variability in serum concentration is a function of variability of each process involved. This should be noted in explanation of effect of molecular features of drugs on their plasma concentration profile.

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