Plasma Concentrations after Three Different Doses of Topical Isotretinoin

Santana, Davi Pereira de; Bun, H.; Joachim, J; Durand, Alain; Reynier, Jean-Pierre

doi:10.1159/000211288

Cited by 6 publications

(2 citation statements)

References 10 publications

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“…1c). Such a concentration in the microenvironment of melanocytes is unlikely since melanocytes are very close to the superficial dermal blood vessels and no modulation of plasma retinoid levels can be detected following topical retinoid application [29,30], which indicates that very low retinoid concentrations may reach these blood vessels following topical application of 0.05% retinoids. However, we cannot rule out the possibility that the decreased activity of tyrosinase observed in vitro (fig.…”

Section: Discussionmentioning

confidence: 99%

The Potential Depigmenting Activity of Retinaldehyde

Sorg

Kasraee²,

Salomon³

et al. 2013

Dermatology

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Background: Retinoids have been reported to exert depigmenting activity. Unlike most depigmenting agents that target tyrosinase, they are not phenolic agents and may act via different mechanisms. Objectives: We analysed the properties of retinaldehyde (RAL), a precursor of retinoic acid (RA), as a skin-lightening agent in various models. Methods: The viability and the depigmenting properties of RAL were assessed in murine melanocytes, in human reconstructed epidermis, and in mice and guinea pigs. The melanin content and cytotoxicity were assessed in melanocytes; in 3-dimensional models, the melanin concentration and the number of active melanocytes were determined. Results: RAL was taken up by melanocytes and mostly metabolised to retinol and retinyl esters, and to a lesser extent to RA. RAL decreased the melanin concentration of guinea pig ears and mouse tails by 54 and 74%, respectively, and decreased the number of active melanocytes by 42 and 77%, respectively. In reconstructed epidermis the melanin concentration was increased by 52%, whereas the number of active melanocytes decreased by 44%. Conclusion: RAL exerts a significant depigmenting activity with a mode of action that looks different from that of RA. Our data suggest a skin-lightening effect related to a melanolytic action (i.e. a decrease in melanin concentration, whatever the mechanism) rather than to melanocytotoxicity, besides other still unknown actions of RAL on melanocytes.

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Section: Discussionmentioning

confidence: 99%

The Potential Depigmenting Activity of Retinaldehyde

Sorg

Kasraee²,

Salomon³

et al. 2013

Dermatology

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“…Application of topical retinoids has been shown to induce a manifold increase of the epidermal concentration 23,[38][39][40][41][42][43] although no significant increase of plasma retinoids was observed; [44][45][46][47] this indicates that topical retinoids could have a pharmacologic action to the skin, as opposed to the biological effects of physiological cutaneous retinoids. Thus, topical retinoids have powerful therapeutic potential in the treatment of various diseases.…”

Section: The Biology Of Topical Retinoidsmentioning

confidence: 99%

Proposed mechanisms of action for retinoid derivatives in the treatment of skin aging

Sorg

Kuenzli

Kaya

et al. 2005

J of Cosmetic Dermatology

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Skin aging (intrinsic aging) and photoaging (extrinsic aging) involve a similar process that leads to the typical creased appearance of the skin, with the progressive loss of its physical and biologic properties. Photoaging is a premature skin aging caused by long-term exposure to the ultraviolet B radiations of the sun, and is more frequently associated to skin cancer than intrinsic aging. Retinoids are natural and synthetic vitamin A derivatives. They are lipophilic molecules and penetrate the epidermis easily. Their biologically active forms can modulate gene expression by binding to nuclear receptors and then to specific DNA sequences. Because of their ability to modulate genes involved in cellular differentiation and proliferation, they appear as good candidates to treat and prevent photoaging. Hyaluronate and collagen, two major constituents of the dermis, are progressively decreased and altered during aging. Various retinoids were shown to increase their synthesis and concentration in the skin and reduce their rate of degradation. Furthermore, retinoids share a common chemical structure containing several conjugated double bonds that enable them to trap free radicals and absorb UV radiations from the sun, thereby protecting cellular targets such as DNA, lipid membranes, or proteins by preventing direct photochemical damage or UV-induced oxidative stress. Therefore, retinoids may be beneficial in treating skin aging and photoaging because of their biologic, chemical, and physical properties, which act at several levels.

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Clinical Pharmacokinetics and Drug Metabolism of Tazarotene

Tang-Liu

Matsumoto

Usansky

1999

Clinical Pharmacokinetics

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Tazarotene (AGN 190168) is a new acetylenic retinoid which is effective for the topical treatment of patients with stable plaque psoriasis and mild to moderate acne vulgaris. Topical gel application provides direct delivery of tazarotene into the skin. At 10 hours after a topical application of 0.1% tazarotene gel to the skin of healthy individuals and patients with psoriasis, approximately 4 to 6% of the dose resided in the stratum corneum and 2% of the dose distributed to the viable epidermis and dermis. Tazarotene is rapidly hydrolysed by esterases to its active metabolite, tazarotenic acid. Tazarotenic acid does not accumulate in adipose tissue, but undergoes further metabolism to its sulfoxide and to other polar metabolites and is rapidly eliminated via both urinary and faecal pathways with a terminal half-life of about 18 hours. Percutaneous absorption is similar between healthy individuals and patients with facial acne, leading to plasma concentrations below 1 microg/L. The systemic bioavailability of tazarotene (measured as tazarotenic acid) is low, approximately 1% after single and multiple topical applications to healthy skin. In patients with psoriasis under typical conditions of use, systemic bioavailability increased during the initial 2 weeks of treatment from 1% (single dose) to 5% or less (steady state). The increased bioavailability is probably related to decreases in plaque elevation and scaling due to successful treatment, resulting in a less effective skin penetration barrier to tazarotene. Steady-state concentrations of tazarotenic acid are achieved within 2 weeks of topical treatment in both healthy and psoriatic skin types. The large variability in plasma concentrations observed in patients with psoriasis is probably because of the large differences in lesional skin condition, the amount of drug applied and the surface area of application. There was no significant drug accumulation in the body with long term treatment of patients with psoriasis. Topical administration of tazarotene requires dosages much smaller than those usually required for oral retinoids, such as isotretinoin, acitretin and etretinate, and it delivers the drug directly into the target skin tissues. The low systemic absorption and rapid systemic elimination of tazarotene and tazarotenic acid results in limited systemic exposure. Thus, topical tazarotene has a low potential for systemic adverse effects and is effective in the treatment of patients with acne and psoriasis.

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Plasma Concentrations after Three Different Doses of Topical Isotretinoin

Cited by 6 publications

References 10 publications

The Potential Depigmenting Activity of Retinaldehyde

The Potential Depigmenting Activity of Retinaldehyde

Proposed mechanisms of action for retinoid derivatives in the treatment of skin aging

Clinical Pharmacokinetics and Drug Metabolism of Tazarotene

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