Pharmacodynamics and dermatopharmacokinetics of betamethasone 17-valerate: assessment of topical bioavailability.
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.
Wiedersberg
S
S
Department of Pharmacy & Pharmacology, University of Bath, Claverton, Bath, BA2 7AY, UK.
Naik
A
A
Leopold
C S
CS
Guy
R H
RH
D000279:Administration, Cutaneous; D000328:Adult; D001624:Betamethasone Valerate / Q000493:pharmacokinetics*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014677:Pharmaceutical Vehicles; D015203:Reproducibility of Results; D012867:Skin / Q000098:blood supply / Q000378:metabolism*; D012869:Skin Absorption; D013048:Specimen Handling / Q000379:methods; D053832:Surgical Tape; D013816:Thermodynamics; D014661:Vasoconstriction; D055815:Young Adult
D005938:Glucocorticoids; D014677:Pharmaceutical Vehicles; D001624:Betamethasone Valerate