Transdermal drug pharmacokinetics in man: Interindividual variability and partial prediction

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 an...

Full description

Saved in:
Bibliographic Details
Published in:International journal of pharmaceutics 2009-02, Vol.367 (1), p.1-15
Main Authors: Farahmand, Sara, Maibach, Howard I.
Format: Article
Language:English
Subjects:
Administration, Cutaneous
Biological Availability
Dose-Response Relationship, Drug
Humans
Interindividual variation
Pharmaceutical Preparations - administration & dosage
Pharmaceutical Preparations - blood
Pharmacokinetics
Predictive Value of Tests
QSPR
Regression Analysis
Skin Absorption
Therapeutic Equivalency
Transdermal drug delivery
Transdermal patch
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 ( C max) 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 C max, is inversely correlated with drugs molecular weight and lipophilicity in the range of 200 < MW < 400 and 1.6 < log K oct < 4.3. Multiple regression analysis of C max 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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2008.11.020