Acitretin

The free acid analogue of the antipsoriatic agent etretinate (103) is prepared in substantially the same way as the parent compound. Thus, the aldehyde group in 98 is converted finally to the pho.sphonate (101) by sequential reduction (99), conversion to the chloride (100), and finally reaction with triethyl phosphite. Condensation of the ylide from 101 with the benzaldehyde 102 gives etretinate (103) saponification affords acitretin (104) [25]. 

Acitretine ch3o x x Oral 0.25-1.0 mg/kg/d Psoriasis (erythrodermic, pustular, and severe recalcitrant) Palmoplantar keratoderma pustulosis palmoplantaris, icthyosis, Darier s disease, pityriasis rubra pilaris, lichen ruber planus... 

Several UVB and systemic therapy combinations have shown efficacy. These include UVB with acitretin (ReUVB) and UVB with methotrexate, and will be discussed later. 

Systemic therapies are seldom used for mild to moderate psoriasis, and are generally reserved for patients with moderate to severe psoriasis.17 29 Oral agents include sulfasalazine, acitretin, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, and hydroxyurea. Parenteral agents include the biologic response modifiers alefacept, efalizumab, etanercept, infliximab, and many others, currently at various stages of research or approval for psoriasis. 

Acitretin is an oral retinoid that is likely safer than methotrexate or cyclosporine, especially when considering continuous use over many years.21 The initial dose is 25 mg/day which can be increased to a maximum of 75 mg/day if needed.17 When acitretin is used concurrently with phototherapy (ReUVB or RePUVA), there appears to be a synergistic treatment effect, and the number and duration of phototherapy sessions needed to achieve clearance is reduced.21 RePUVA is a well-established... 

Acitretin Monitor serum lipids and liver function tests. 

Sulfasalazine is an antiinflammatory agent that inhibits 5-lipoxygenase. It is used selectively as an alternative treatment, particularly in patients with concurrent psoriatic arthritis. When used alone, it is not as effective as methotrexate, PUVA, or acitretin. However, it has a relatively high margin of safety. The usual oral dose is 3 to 4 g/day for 8 weeks. Its adverse effects are similar to other sulfonamide antibiotics. 

Sequential therapy involves rapid clearing of psoriasis with aggressive therapy (e.g., cyclosporine), followed by a transitional period in which a safer drug such as acitretin is started at maximal dosing. Subsequently, a maintenance period using acitretin in lower doses or in combination with UVB or PUVA can be continued. 

Acid yellow (Aquashade), herbicide/algicide for aquaculture in U.S., 3 214t Acitretin, 25 790 a-c Josephson effect, 15 750 Aclame, 24 232 ac losses, 23 845-846 Acne, vitamin A treatments for, 25 789 cis-Aconitic acid, in citric acid cycle, 6 633 Aconitine, 2 103... 

A. H. Schmitt-Hoffmann, S. Dittrich, E. Saulnier, P. Schenk, R. C. Chou, Mechanistic Studies on the Ethyl-Esterification of Acitretin by Human Liver Preparations in vitro, Life Sci. 1995, 57, PL407-PL412. 

K. M. Knights, R. Gasser, W. Klemisch, In vitro Metabolism of Acitretin by Human Liver Microsomes Evidence for an Acitretinoyl-Coenzyme A Thioester Conjugate in the Transesterification to Etretinate , Biochem. Pharmacol. 2000, 60, 507-516. 

Other drugs Acetazolamide, acetosulfone, acetylcysteine, acitretin, allopurinol, aminoglutehimide, benzaflbrate, brompheniramine, calcium dobe-silate, chloropheniramine, chlorpropamide, colchicine, deferiprone, dapsone, flutamide, glibenclamide, hydroxychloroquine, mebhydro-lin, meprobamate, metapyrilene, methazolamide, metochlopramide, prednisone, promethazine, retinoic acid, riluzole, ritodrine, tolbutamide, yohimbine... 

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 transesterifled to form etretinate, a retinoid that is stored in adipose tissue, resulting in a much longer half-life (3-4 months or longer). 

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. 

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