Pharmacokinetic studies for the development of transdermal drug delivery systems

Abstract

This thesis mainly describes a series of Phase I pharmacokinetic studies conducted on the TDS®d elivery systemw hich combinedw ith lidocaine,t estosteronea, nd a new drug, Melanotan-I for the transdermal drug delivery. Pharmacodynamic studies have also been carried out in certain areas to support the pharmacokinetics. The initial challenge was the development and validation of a method to analyse lidocaine in human plasma by LCMS-MS. The sensitivity and reliability of the developed method has enabled the analysis of lidocaine plasma levels from the TDS®- Lidocaine study. The results from the study have shown that the TDS® system has been able to deliver the drug effectively through the skin. This finding had a positive impact on the future development of the TDS® system in combination with other drugs. The combination of the TDS® system with testosterone had been successfully tested in 12 healthy male subjects. TDS®-Testosterone was found to be bioequivalent to Androgel®. This result gave an insight into further development of this preparation if it is to be regarded as an alternative treatment for hypogonadism. Various methods of correcting for endogenous testosterone were performed on the data and the influence on bioequivalence was studied. Testosterone was used as a model drug and used to explore potential guidelines for the bioequivalence assessment of endogenous compounds. Finally, the TDS® system has been combined with a new, peptide derived drug, Melanotan-I (MT-I). This drug is currently under development for the cosmetic purposes and the treatment of various skin conditions related to sun allergies. A dose escalation study of TDS®-Melanotan for the protective tanning of skin was carried out and the result was presented. In addition, in vivo techniques, such as microdialysis and tape stripping, have also been explored to investigate the feasibility of measuring pharmacokinetic of a transdermal drug instead of using the conventional systemic measurements.