Conflicts of interest None declared.
Pharmacodynamics and dermatopharmacokinetics of betamethasone 17-valerate: assessment of topical bioavailability
Article first published online: 8 SEP 2008
© 2008 The Authors. Journal Compilation © 2008 British Association of Dermatologists
British Journal of Dermatology
Volume 160, Issue 3, pages 676–686, March 2009
How to Cite
Wiedersberg, S., Naik, A., Leopold, C.S. and Guy, R.H. (2009), Pharmacodynamics and dermatopharmacokinetics of betamethasone 17-valerate: assessment of topical bioavailability. British Journal of Dermatology, 160: 676–686. doi: 10.1111/j.1365-2133.2008.08757.x
- Issue published online: 17 FEB 2009
- Article first published online: 8 SEP 2008
- Accepted for publication 14 May 2008
- topical bioavailability;
- topical bioequivalence;
- vasoconstrictor assay
Background The bioavailability of most topically delivered drugs is difficult to quantify, but is generally believed to be very low. With the exception of the vasoconstrictor assay for corticosteroids, no methodology to quantify the rate and extent of drug delivery to the skin has been validated. Recent research has examined the dermatopharmacokinetic (DPK) technique, which is based on stratum corneum (SC) tape-stripping.
Objective To compare the in vivo bioavailability of different topical formulations of betamethasone 17-valerate (BMV) using the vasoconstrictor assay and the DPK method.
Methods BMV was formulated in different vehicles and the drug concentration was adjusted to either (i) equal thermodynamic activity, or (ii) a range of values up to that corresponding to 80% of maximum thermodynamic activity. Vasoconstriction, an accepted and widely used method to determine bioavailability and bioequivalence of topical steroids, was quantified with a chromameter over 24 h post-removal of the formulation. Drug uptake into the SC was assessed by tape-stripping.
Results BMV at the same thermodynamic activity in different vehicles provoked similar skin blanching responses, while DPK profiles distinguished between the formulations. Further, skin blanching responses and drug uptake into the SC clearly depended upon the absolute BMV concentration applied. However, while the saturable nature of the pharmacodynamic response was clear, the tape-stripping method distinguished unequivocally between the different formulations and different concentrations.
Conclusions The DPK approach offers a reliable metric with which to quantify transfer of drug from the vehicle to the SC, and may be useful for topical bioavailability and bioequivalence determinations.