Absorption and Local Action of Methotrexate in Human and Mouse Skin

Stewart, William D.

doi:10.1001/archderm.1972.01620120045009

Cited by 34 publications

(16 citation statements)

References 15 publications

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“…Topical MTX seems to be well‐tolerated at the skin surface causing no or only mild to moderate clinical skin irritation . However, previous literature has debated whether MTX requires systemic activation or will be effective after topical delivery . Until now, two randomized controlled studies and five clinical observational studies have demonstrated efficacy of topical MTX‐treatments for patients with psoriasis.…”

Section: Discussionmentioning

confidence: 99%

“…MTX has previously been delivered topically by chemical and physical barrier penetration technologies including microemulsions , liposomes , iontophoresis , electroporation , microneedles , intracutaneous injections , diode laser , and full‐ablative erbium yttrium aluminium garnet laser (Er:YAG laser) . In addition, we recently demonstrated in vitro that it is possible to deliver MTX topically by exposure to ablative fractional laser (AFXL) .…”

Section: Introductionmentioning

confidence: 99%

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Fractional laser-assisted drug delivery: Laser channel depth influences biodistribution and skin deposition of methotrexate

et al. 2016

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fractional laser-assisted drug delivery: Laser channel depth influences biodistribution and skin deposition of methotrexate

et al. 2016

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“…On the contrary, their combination was seen to be more effective than either drug alone. Furthermore, local administration of MTX, giving rise to a similar tissue concentration obtained by systemic treatment, has been shown to be ineffective in psoriasis (6,8), indicating that MTX does not cause apoptosis of leucocytes residing in psoriatic lesions. This strongly supports the notion that the therapeutic effect of MTX treatment is due, at least in part, to downregulation of adhesion molecules.…”

Section: Discussionmentioning

confidence: 99%

“…thymidine) synthesis and, thereby, inhibition of DNA synthesis (5). Local administration of MTX to psoriatic plaques that gives rise to a similar tissue concentration obtained by systemic treatment has been equivocal in efficacy (6–9). This indicates that the beneficial effect of MTX is not due to a direct inhibition of keratinocyte proliferation (10).…”

Section: Introductionmentioning

confidence: 99%

Methotrexate markedly reduces the expression of vascular E‐selectin, cutaneous lymphocyte‐associated antigen and the numbers of mononuclear leucocytes in psoriatic skin

Sigmundsdóttir

Johnston

Guðjónsson

et al. 2004

Experimental Dermatology

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A positive correlation between disease severity and the frequency of cutaneous lymphocyte-associated antigen (CLA)-positive T cells in the blood of untreated patients with psoriasis has been previously observed. A dose-dependent inverse relationship between disease severity and the frequency of circulating CLA(+) T cells in psoriasis patients on methotrexate (MTX) treatment is reported. Circulating T cells from a patient with psoriasis were monitored for CLA expression on a daily basis for 5 weeks. A decrease in the intensity and frequency of CLA(+) mononuclear leucocytes was consistently observed in the blood during the first 3-4 days after each MTX intake, but the CLA expression increased thereafter until the next weekly dose was taken. The MTX treatment of this patient was then discontinued for 16 days, and a marked subjective exacerbation was reported within 9 days, which was confirmed objectively (laser Doppler perfusion imaging) after 11 and 16 days. Biopsies taken 4 days after the last MTX intake showed only a few mononuclear leucocytes in lesional skin, but the exacerbation coincided with a marked increase in CLA expression by mononuclear blood leucocytes, followed by an increase in endothelial E-selectin and a striking influx of CLA(+) mononuclear cells into lesional skin. Conversely, a clinical improvement after the patient resumed the MTX treatment was associated with reduction in CLA expression by mononuclear cells in the blood, downregulation of endothelial E-selectin and an approximate threefold decrease in mononuclear leucocyte infiltration of lesional skin. No MTX-associated changes were detected in the expression of very late antigen-4, vascular cell-adhesion molecule-1 nor the late activation marker CD25. It is concluded that MTX decreases the expression of CLA and E-selectin and that this may be a major mechanism for the therapeutic effect of MTX on psoriatic skin lesions.

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“…Po podaniu dootrzewnowym i domięśniowym zostaje całko-wicie wchłonięty. Przyswajanie metotreksatu przez skórę zwierząt lub ludzi wynosi maksymalnie 24%, w większości badań in vitro -od 0,05 do 4,0% dawki początkowej [5][6][7][8].…”

Section: Wstępunclassified

Methotrexate – Genotoxic and teratogenic for medical staff of oncology wards?

Kupczewska-Dobecka¹

2015

Med Pr

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StreszczenieJednym z najczęściej stosowanych leków cytostatycznych jest metotreksat (MTX) należący do antagonistów kwasu foliowego. Jest to substancja w Unii Europejskiej niezaklasyfikowana jako rakotwórcza, a Międzynarodowa Agencja Badań nad Rakiem (International Agency for Research on Cancer -IARC) oceniła, że nie ma dowodów na jej oddziaływanie rakotwórcze u ludzi i zwierząt. Mimo to MTX znalazł się na listach leków niebezpiecznych stosowanych w chemioterapii, głównie ze względu na właściwości genotoksyczne oraz działanie teratogenne, powodowanie toksyczności rozwojowej i szkodliwy wpływ na rozrodczość. Metotreksat wykryto w powietrzu oddziału szpitalnego podczas przygotowywania leku, na poziomie 0,3 µg/m 3 , a także na rękawicach ochronnych oraz czyszczonych powierzchniach pokoi przygotowawczych. Stężenie MTX na polietylenowym pokryciu wyciągu wentylacyjnego wynosiło 645 µg/m 2 . W większości prowadzonych projektów badawczych zidentyfikowano MTX w moczu pracowników opieki medycznej, farmaceutów i personelu pielęgniarskiego, a także pracowników służby zdrowia, którzy byli narażeni w wyniku wtór-nego zanieczyszczenia powierzchni roboczych, odzieży czy pojemników. Najwyższe skumulowane stężenie MTX w 112 próbkach moczu wynosiło 1416 µg u pracowników podłączających i przygotowujących wlewy u pacjentów. Badania przeprowadzone w aptekach wykazały obecność MTX w 60% pobranych prób, a jego maksymalne stężenie wynosiło 15 ng/cm 2 powierzchni tacy do odliczania tabletek. Dotychczas nie zostały ustalone obowiązujące prawnie wartości najwyższych dopuszczalnych stężeń (NDS) metotreksatu w środowisku pracy. Dopuszczalne poziomy narażenia zawodowego niektórzy producenci MTX ustalili w granicach 0,0003-0,0025 mg/m 3 . Naglącą potrzebą jest ustalenie wartości normatywnych. Należy podkreślić, że substancja wchłania się przez skórę, co może istotnie zwiększać narażenie, a pomiar jej stężenia w środowisku pracy może nie wystarczać do oszacowania rzeczywistego narażenia. Med. Pr. 2015;66(2):265-275 Słowa kluczowe: metotreksat, narażenie zawodowe, cytostatyki, najwyższe dopuszczalne stężenie Abstract Methotrexate (MTX) is one of the most widely used cytostatic drugs belonging to the folic acid antagonists. It is a substance non-classified as a carcinogen in the European Union and by the International Agency for Research on Cancer (IARC) as there is no evidence of its carcinogenicity to humans and animals. Nevertheless, MTX has been placed on the list of dangerous drugs used in chemotherapy, mainly due to genotoxic and teratogenic effects, causing developmental toxicity and reproductive toxicity. Methotrexate was determined in the hospital ward air during the preparation of a medicament at a level of 0.3 mg/m 3 , as well as on protective gloves and preparatory room surfaces. In most research projects MTX was identified in the urine of health care workers, pharmacists and nursing staff. The highest cumulative concentration of MTX in 112 urine samples was 1416 mg in workers preparing infusions for patients. Studies carried out in ph...

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Absorption and Local Action of Methotrexate in Human and Mouse Skin

Cited by 34 publications

References 15 publications

Fractional laser-assisted drug delivery: Laser channel depth influences biodistribution and skin deposition of methotrexate

Fractional laser-assisted drug delivery: Laser channel depth influences biodistribution and skin deposition of methotrexate

Methotrexate markedly reduces the expression of vascular E‐selectin, cutaneous lymphocyte‐associated antigen and the numbers of mononuclear leucocytes in psoriatic skin

Methotrexate – Genotoxic and teratogenic for medical staff of oncology wards?

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