Skin and systemic pharmacokinetics of tacrolimus following topical application of tacrolimus ointment in adults with moderate to severe atopic dermatitis

Undre, Nasrullah; Moloney, Fergal J.; Ahmadi, Shahnaz Delbarpoor; Stevenson, Paul; Murphy, Gillian

doi:10.1111/j.1365-2133.2008.08974.x

Cited by 67 publications

(54 citation statements)

References 10 publications

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“…No studies on the use or effect of topical tacrolimus during pregnancy have been published. Systemic absorption of topical tacrolimus is, however, very low in both 0.1% and 0.03% concentrations due to the large size of the molecule, although a very impaired skin barrier as seen in Netherton syndrome may allow absorption . Taken together with the large experience on systemic use of calcineurin inhibitors in organ transplant patients, available data suggest that the risk of congenital defects is not increased.…”

mentioning

confidence: 99%

European task force on atopic dermatitis position paper: treatment of parental atopic dermatitis during preconception, pregnancy and lactation period

Vestergaard

Wollenberg

Barbarot

et al. 2019

Acad Dermatol Venereol

173

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Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults, including a large number of adults of reproductive age. Several guidelines for the treatment of AD exist, yet specific recommendations for the treatment of pregnant or lactating women and for adults planning to have a child are often lacking. This position paper from the European Task force on Atopic Dermatitis (ETFAD) is based on up‐to‐date scientific literature on treating pregnant and lactating women as wells as adults with AD planning to have a child. It is based on the expert opinions of members of the ETFAD and on existing safety data on the proposed treatments, many of which are derived from patients with other inflammatory diseases or from transplantation medicine. For treating future parents, as well as pregnant and lactating women with AD, the use of topical treatments including moisturizers, topical corticosteroids, tacrolimus, antiseptics such as chlorhexidine, octenidine, potassium permanganate and sodium hypochlorite (bleach) is deemed to be safe. Ultraviolet (UV) therapy may also be used. Systemic treatment should be prescribed only after careful consideration. According to the opinion of the ETFAD, treatment should be restricted to systemic corticosteroids and cyclosporine A, and, in selected cases, azathioprine.

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mentioning

confidence: 99%

European task force on atopic dermatitis position paper: treatment of parental atopic dermatitis during preconception, pregnancy and lactation period

Vestergaard

Wollenberg

Barbarot

et al. 2019

Acad Dermatol Venereol

173

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“…In our study, we analyzed the serum levels of three receptors on CTL and their relative chemokines based on a large sample size. First, local treatment with calcineurin inhibitors did not change the levels of chemokines in serum, which may be due to the minimal systemic exposure of tacrolimus following topical application of tacrolimus ointment . Elevated levels of CCL5, CXCL8 and CXCL10 were observed in the serum of active vitiligo patients, and the levels of CCL5 and CXCL8 were also increased in stable vitiligo patients compared with controls, suggesting that these chemokines may play important roles in the progression and maintenance of vitiligo.…”

Section: Discussionmentioning

confidence: 95%

Role of chemokines and the corresponding receptors in vitiligo: A pilot study

Yang

Lei

et al. 2017

The Journal of Dermatology

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To determine the levels and sources of chemokines in the serum and epidermis of vitiligo patients, we examined 80 active patients, 80 stable patients and 40 healthy controls. First, the serum levels of candidate chemokines were measured by Luminex assay, and levels of CCR5, CXCR1 and CXCR3 were measured in peripheral mononuclear cells (PMBC) by flow cytometry. Then, the local epidermis levels of elevated chemokines in vitiligo were tested by Luminex. Finally, the mRNA and protein expression levels of elevated chemokines in HaCaT cells stimulated with interferon (IFN)-c or tumor necrosis factor (TNF)-a were tested by quantitative real-time polymerase chain reaction and Luminex. The serum levels of CCL5, CXCL8 and CXCL10 in active vitiligo were significantly elevated compared with those in stable vitiligo patients. Furthermore, the levels of CCL3 and CCL4 had weak and positive correlations with the Vitiligo Area Scoring Index. In the peripheral blood of active vitiligo patients, the percentages of CD3 cells were significantly increased compared with those in stable vitiligo and healthy controls. In the epidermis of lesions, the expression levels of CCL5 and CXCL10 in active vitiligo were significantly increased. In addition, the mRNA and protein levels of CCL5, CXCL8 and CXCL10 were significantly elevated in HaCaT cells after stimulation with TNF-a or IFN-c. The CCR5/CCL5 and CXCR3/CXCL10 axes may play an important role in the progression and maintenance of vitiligo. Moreover, keratinocytes stimulated with TNF-a and IFN-c may be a primary source of CCL5 and CXCL10.

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“…For topical uses of tacrolimus that do not increase systemic blood concentration of the content, systemic tacrolimus levels were negligible when compared with using systemic agents (24,25). Therefore, it is suggested that unknown systemic factors may play a critical role in the local skin healing process, such as diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

Topical tacrolimus does not negatively impact acute skin wound healing

Namkoong

Chung

Yoo

et al. 2013

Experimental Dermatology

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Despite the increasing use of topical tacrolimus, there is little information about its effect on skin wound healing. To determine effects on acute cutaneous wound healing, two fullthickness skin wounds were imparted on the backs of 45 hairless mice, which were then divided into vehicle-, topical tacrolimusand topical steroid-treated group. Each drug was topically applied once daily. The wound area was assessed by using dermoscopic images every two days after wounding. At 3, 7 and 11 days after wounding, 10 wounds in each group were collected for semiquantitative analysis of histological features including re-epithelialization, polymorphonuclear leucocytes, fibroblasts and collagen. We also checked the mRNA expression levels of EGF, TGF-b, TNF-a and IL-1a. While topical application of clobetasol propionate was found to delay re-epithelialization and infiltration of polymorphonuclear leucocyte, topical treatment with tacrolimus showed patterns similar to that of the vehicle. In the tacrolimus-treated group, mRNA expression levels of IL-1a and TGF-b were slightly decreased, while the others were similar with the vehicle-treated group. Unlike steroid, topical tacrolimus, therefore, did not disturb the wound healing process in a murine skin wound model.

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Skin and systemic pharmacokinetics of tacrolimus following topical application of tacrolimus ointment in adults with moderate to severe atopic dermatitis

Abstract: Tacrolimus was primarily partitioned in the skin, with minimal systemic absorption after topical application, in patients with atopic dermatitis.

Cited by 67 publications

References 10 publications

European task force on atopic dermatitis position paper: treatment of parental atopic dermatitis during preconception, pregnancy and lactation period

European task force on atopic dermatitis position paper: treatment of parental atopic dermatitis during preconception, pregnancy and lactation period

Role of chemokines and the corresponding receptors in vitiligo: A pilot study

Topical tacrolimus does not negatively impact acute skin wound healing

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