Absorption and local action of methotrexate in human and mouse skin

Stewart, W. D.

doi:10.1001/archderm.106.3.357

Cited by 23 publications

(26 citation statements)

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“…We support the hypothesis of Stewart which suggests that the biological effects of methotrexate in psoriasis occur by direct drug action on the psoriasis plaque, but are mediated by systemic action at a site distant from skin (11).…”

Section: Discussionsupporting

confidence: 86%

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Differences in the Biochemical Activity in Hairless Mouse Skin and Other Organs after Systemic and Topical Methotrexate Treatment

Yoshino

Maibach

1989

The Journal of Dermatology

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DNA synthesis in epidermis, spleen, small intestine, and muscle of the hairless mouse was measured after systemic and topical methotrexate dosing. Mice intraperitoneally injected with methotrexate (5 mg/Kg) incorporated 3H-UdR in epidermis at 90% of baseline at 3 hrs, and the incorporation was not suppressed at 24 hrs. Muscle DNA synthesis was not suppressed. In the spleen and small intestine, incorporation was greatly suppressed to 10% at 3 hrs. On the other hand, after topically applied methotrexate (25 mg/Kg) treatment, epidermis and muscle were 60-90% of baseline at 3-24 hrs and spleen and small intestine were 5-10% at 3-6 hrs. In a prolonged time schedule study (4 days), epidermal incorporation after intraperitoneally applied methotrexate (5 mg/Kg) showed no suppression, but was instead stimulated to 180% at 2 days. 5-Fluorouracil, a thymidine kinase inhibitor in antitumor agents, was topically applied (25 mg/Kg) and compared for DNA synthesis. The incorporation of 3H-UdR was drastically suppressed at 3 hrs. The results suggest that methotrexate is percutaneously absorbed, but does not extensively suppress epidermal DNA synthesis in hairless mice, although it does suppress spleen and intestinal DNA synthesis.

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Section: Discussionsupporting

confidence: 86%

“…Topical absorption of MTX by hairless mouse was previously shown by Stweart et al (11). Methotrexate topical absorption through human skin has been reported; methotrexate has been detected in the urine of psoriatic patients treated topically with methotrexate cream (8) and methotrexate in dimethylsulfoxide (9).…”

Section: Discussionmentioning

confidence: 95%

Differences in the Biochemical Activity in Hairless Mouse Skin and Other Organs after Systemic and Topical Methotrexate Treatment

Yoshino

Maibach

1989

The Journal of Dermatology

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“…However, topical MTX delivery by other physical enhancement strategies including iontophoresis, microneedles, intracutaneous injections, diode laser and full-ablative Er:YAG laser has been studied in vitro in passive diffusion models [3][4][5]32,33] and in vivo in animals and humans [4,6,8,9,24,25,29]. In vitro studies generally reported lower skin deposition than the 10-fold increase by AFXL in our study, whereas one study of full-ablative Er:YAG laser demonstrated a maximum 19-fold increased MTX concentration in skin [3].…”

Section: Discussionmentioning

confidence: 99%

“…delivery of MTX has previously been investigated by chemical enhancement strategies and physical barrier disruption techniques such as iontophoresis, microneedles, diode laser, fullablative Erbium Yttrium Aluminum Garnet (Er:YAG) laser, and intracutaneous injections [2][3][4][5][6][7][8]. In vitro studies of these techniques have shown that MTX can be delivered topically [3][4][5].…”

mentioning

confidence: 99%

“…In vitro studies of these techniques have shown that MTX can be delivered topically [3][4][5]. However, the efficacy of topical MTX in in vivo studies on animals and human psoriasis patients has shown conflicting results, which may be explained by imprecise drug delivery [6][7][8][9][10]. Therefore, there is a need to investigate new approaches to deliver MTX topically.…”

mentioning

confidence: 99%

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