Cutaneous absorption of retinyl palmitate and acetate in healthy volunteers

H. Egekvist1, P. Jacobsen2, P. Bjerring1
Department of Dermatology, Aarhus University Hospital1 and Department of Pharmacology, Aarhus University2, Aarhus, Denmark.

Vitamin A derivatives (retinoids) have been demonstrated to stabilize
cutaneous free radicals. Retinoids have subsequently been used in re-
duction of cutaneous photo aging and photocarcinogenisis. Retinoic
acid has been related to decreased epidermal hyperplasia, to increased
dermal collagen content, and to decreased collagenase activity. Compli-
ance to daily use of topically applied retinoic acid is however, de-
creased by side effects: burning and stinging sensation, development of
erythema and papules.
Therapeutic use of retinyl esters has been hampered by lack of cutane-
ous absorption. The development of percutaneous drug delivery by
liposomes has however, offered new possibilities.
Figure 1.
Sonographic picture (subject 01) before application of retinyl cream. The aim was to investigate cutaneous absorption of the esters retinyls Superficially is the high-echogenic epidermal entrance echo, below palmitate and retinyl acetate from topical repetitive cream application. is the dermal echo of lower echogenicity. Most profound is the sub-cutaneous layer with absent echo. Material and methods

Fifteen healthy women, age (45 ±2.1)(mean ±SD) years participated in
the present investigation. Retinyl cream (Beauté Pacifique, Denmark)
(0.3 ml) with 10.000 IU retinyl/g, 60% retinyl palmitate and 40% reti-
nyl acetate, or placebo cream were applied to a skin area of 36 cm2 of
the medical side of the upper arms once daily in five consecutive days.
The creams were applied placebo-controlled, double-blinded and ran-
domized. High frequency ultrasound (20 MHz) examination of the skin
was performed prior to and after skin application period.
Side effects as stinging, burning, redness and scaling were scored from
0 (none) to 3 (severe).
Sonographic picture (subject 01) after application period of reti- Suctions blisters from all treated skin areas were made and the blister nyl cream. The dermal echo demonstrates increased markedly fluids were by High Performance Liquid Chromatography (HPLC) analyzed for concentrations of retinyl palmitate, retinyl acetate and Conclusion
The sonographic skin measurement demonstrates an increased From sonographic skin examination no significant difference in thick- dermal density without change in low-echogenic density, i.e. water ness of epidermal entrance echo, thickness of dermal echo or of total content. This may reflect either increased cellularity or increased fiber content. The present data demonstrates a cutaneous uptake of retinyl palmitate from a cream vehicle and suggests a subsequent However, a significant percent increase in mean dermal sonographic density from the skin treated with retinyl cream (25.2% ±24.8%)(mean ±SD) compared to placebo cream (10.4% ±22.2%) was demonstrated. References
No significant percent change in low-echogenic density between skin treated with retinyl cream and placebo cream was demonstrated. 1. Kligman AM et al. Topical tretinoin for photoaged skin. J Am Compared to the placebo treated skin the retinol concentration (247.4 ± 89.4 ng/ml)(mean ±SD) and the retinyl palmitate concentrations (7.0 ± 2. Sporn MB et al. Mechanism of action of retinoids. J Am. Acad 8.6 ng/ml) were both significantly higher in the suction blister fluid from the skin treated with retinyl containing cream (p<0.05). 3. Schwartz E et al. Topical all-trans retinoic acid stimulates colla- The retinyl acetate concentration in the blister fluid was not signifi- gen synthesis in vivi. J Invest Dermatol 1994;96:975-8. cantly different between the skin applied with cream containing retinyl 4. Ertl GA et al. A comparison of the efficacy of topical tretinoin an low-dose oral isotretinoin emollient cream treatment regimen: One subject initially experienced minimal itch (score 1) at the area Effect of once-weekly and three-times-weekly applications. J Am treated with active cream. No subjects developed erythema of the skin.


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