Influence of a microemulsion vehicle on cutaneous bioequivalence of a lipophilic model drug assessed by microdialysis and pharmacodynamics.
OBJECTIVE
The aim of the study was to investigate the cutaneous bioequivalence of a lipophilic model drug (lidocaine) applied in a novel topical microemulsion vehicle, compared to a conventional oil-in-water (O/W) emulsion, assessed by a pharmacokinetics microdialysis model and a pharmacodynamic method.


METHODS
Dermal delivery of lidocaine was estimated by microdialysis in 8 volunteers. Absorption coefficients and lag times were determined by pharmacokinetic modelling of the microdialysis data. Subsequently, the anaesthetic effect of the treatments was assessed by mechanical stimuli using von Frey hairs in 12 volunteers.


RESULTS
The microemulsion formulation increased the cutaneous absorption coefficient of lidocaine 2.9 times (95% confidence interval: 1.9/4.6) compared with the O/W emulsion-based cream. Also, lag time decreased from 110 +/- 43 min to 87 +/- 32 min (P = 0.02). The compartmental pharmacokinetic model provided an excellent fit of the concentration-time curves with reliable estimation of absorption coefficient and lag time. A significant anaesthetic effect was found for both active treatments compared to placebo (P < 0.02), but the effect did not diverge significantly between the two formulations.


CONCLUSIONS
The microemulsion vehicle can be applied to increase dermal drug delivery of lipophilic drugs in humans. The microdialysis technique combined with an appropriate pharmacokinetic model provides a high sensitivity in bioequivalence studies of topically applied substances.
Kreilgaard
M
M
The Royal Danish School of Pharmacy, Department of Pharmaceutics, Copenhagen. makr@lundbeck.com
Kemme
M J
MJ
Burggraaf
J
J
Schoemaker
R C
RC
Cohen
A F
AF
D000287:Administration, Topical; D000328:Adult; D000465:Algorithms; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004655:Emulsions; D006801:Humans; D008012:Lidocaine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D017551:Microdialysis; D010147:Pain Measurement; D014677:Pharmaceutical Vehicles; D012869:Skin Absorption / Q000502:physiology*; D013810:Therapeutic Equivalency
D000779:Anesthetics, Local; D004655:Emulsions; D014677:Pharmaceutical Vehicles; D008012:Lidocaine