アシトレチン 化学特性,用途語,生産方法
外観
うすい黄色～黄色～黄赤色粉末～結晶
効能
乾癬治療薬, レチノイン酸受容体作動薬
説明
Acitretin is the free acid form of etretinate useful in the treatment of severe psoriasis and other disorders of keratinization. Although the two compounds have virtually the same efficacy and teratogenic side-effects, acitretin is advantageous for child-bearing women, as its shorter half-life reduces the necessary contraception period from two years to only one month after treatment ceases.
化学的特性
Crystalline Solid
使用
Acitretin, a retinoid that binds to nuclear receptors and regulates gene expression, is a potent activator of the α-secretase ADAM10 gene expression and apoptosis inducer via the CD95 signalling pathway. Acitretin is a systemic retinoid drug used in the treatment of severe psoriasis.
適応症
Unlike isotretinoin, acitretin (Soriatane) is not primarily
sebosuppressive. Rather, it promotes normalization
of dysregulated keratinocyte proliferative activity in the
epidermis and is also antiinflammatory. Oral absorption
is optimal when acitretin is taken with a fatty meal; peak
levels are reached approximately 3 hours after ingestion,
while steady-state plasma levels are achieved after
approximately 3 weeks of daily dosing. The mean terminal
elimination half-life of the parent compound is 49
hours. However, when consumed with ethanol, acitretin
may be transesterified to form etretinate, a retinoid that
is stored in adipose tissue, resulting in a much longer
half-life (3–4 months or longer).
世界保健機関（WHO）
Acitretin, a retinol derivative, was introduced in 1989 for the
treatment of severe psoriasis. By the end of 1990, acitretin was confirmed to be
metabolized in part to etretinate. Marketing authorization was suspended
temporarily in France while the product information was modified to conform to the
recommendations issued by the Committee for Proprietary Medicinal Products of
the European Communities. Acitretin remains registered in several countries. See
also WHO comment for etretinate.
一般的な説明
Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards.
Acitretin is a major metabolite of etretinate and belongs to the class of retinoid and is typically used for treating psoriasis. Acitretin inhibits excessive cell growth and keratinisation which are the major symptoms of psoriasis, therefore reducing plaque formation and scaling.
作用機序
Acitretin
(Soriatane) is a synthetic derivative of vitamin A that is particularly effective in
treating the pustular and erythrodermic forms of psoriasis. It is the main metabolite
of etretinate; ingestion of alcohol with acitretin increases the amount of detectable
etretinate. It is accumulated in fatty tissue with a prolonged elimination half-life of
approximately 120 days. Most patients show improvement within 2 to 4 weeks,
although some patients may need as long as 6 months of therapy before a response
is noted.
薬理学
Like other systemic retinoids, acitretin is a serious
teratogen and should not be prescribed for women of
childbearing potential unless no acceptable alternative
is available and the patient has acknowledged in writing
that she understands the need to use two effective
forms of contraception during therapy and for 3 years
following discontinuation of therapy. Because of the
much longer half-life of etretinate, which may be
formed when ethanol is ingested with acitretin, female
patients of childbearing potential must also agree not to
ingest alcohol during treatment and for 2 months following
its discontinuation. Other toxicities are similar
to those of isotretinoin; they include cutaneous irritation
and inflammation, bone and joint pain, hyperlipidemia,
hepatic enzyme elevation, and tendinous and
ligamentous calcifications.Alopecia (hair loss) may also
occur in some patients.
臨床応用
Acitretin is most useful for the treatment of severe
psoriasis, particularly the pustular and erythrodermic
variants. Psoriatic nail changes and arthritis also may respond.
Combining the drug with ultraviolet light therapy
(Re-UVB, in the case of ultraviolet B radiation, or
Re-PUVA, with psoralen plus ultraviolet A radiation)
permits the use of lower doses of both acitretin and ultraviolet
radiation. Other conditions for which the drug
may be especially useful include congenital and acquired
hyperkeratotic disorders, such as the ichthyoses
and palmoplantar keratodermas, and severe lichen
planus.
副作用
Side effects are dose dependent and include elevation of triglycerides,
hepatitis, hair loss, thinning of the nails, cheilitis, xerosis, and stickiness of
the skin. Gemfibrozil (300 mg b.i.d.) corrects elevated lipid levels on this
therapy.
アシトレチン 上流と下流の製品情報
原材料
準備製品