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Clinical pharmacokinetics and drug metabolism of tazarotene - A novel topical treatment for acne and psoriasis

CLINICAL PHARMACOKINETICS 1999年第4期37卷 273-287页

作者： Tang-Liu, DDS Matsumoto, RM Usansky, JI Allergan Pharmaceut Inc Dept Pharmacokinet & Drug Metab Irvine CA 92612 USA

Tazarotene (AGN 190168) is a new acetylenic retinoid which is effective for the topical treatment of patients with stable plaque psoriasis and mild to moderate acne vulgaris. Topical gel application provides direct delivery of tazarotene into the skin. At 10 hours after a topical application of 0.1% tazarotene gel to the skin of healthy individuals and patients with psoriasis, approximately 4 to 6% of the dose resided in the stratum corneum and 2% of the dose distributed to the viable epidermis and dermis. Tazarotene is rapidly hydrolysed by esterases to its active metabolite, tazarotenic acid. Tazarotenic acid does not accumulate in adipose tissue, but undergoes further metabolism to its sulfoxide and to other polar metabolites and is rapidly eliminated via both urinary and faecal pathways with a terminal half-life of about 18 hours. Percutaneaus absorption is similar between healthy individuals and patients with facial acne, leading to plasma concentrations below 1 mu g/L. The systemic bioavailability of tazarotene (measured as tazarotenic acid) is low, approximately 1% after single and multiple topical applications to healthy skin. In patients with psoriasis under typical conditions of use, systemic bioavailability increased during the initial 2 weeks of treatment from 1% (single dose) to 5% or less (steady state). The increased bioavailability is probably related to decreases in plaque elevation and scaling due to successful treatment, resulting in a less effective skin penetration barrier to tazarotene. Steady-state concentrations of tazarotenic acid are achieved within 2 weeks of topical treatment in both healthy and psoriatic skin types. The large variability in plasma concentrations observed in patients with psoriasis is probably because of the large differences in lesional skin condition, the amount of drug applied and the surface area of application. There was no significant drug accumulation in the body with long term treatment of patients with psoriasis.

关键词：痤疮寻常/药物疗法痤疮寻常/代谢投药局部皮肤科用药/投药和剂量皮肤科用药/代谢皮肤科用药/药代动力学烟酸类/投药和剂量烟酸类/代谢烟酸类/药代动力学银屑病/药物疗法银屑病/代谢动物人类

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Bullous diseases: Unapproved treatments or indications

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CLINICS IN DERMATOLOGY 2000年第2期18卷 191-195页

作者： Ruocco, V Ruocco, E Wolf, R Second Univ Naples Dept Dermatol I-80131 Naples Italy

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Topical therapy for acne vulgaris - How do you choose the best drug for each patient?

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POSTGRADUATE MEDICINE 2000年第3期107卷 69-+页

作者： Johnson, BA Nunley, JR Virginia Commonwealth Univ Univ Student Hlth Serv Richmond VA 23298 USA

Although management of acne is sometimes difficult, primary care physicians can offer a number of treatment plans to patients with this skin condition. Comedonal acne usually responds to topical keratolytics, such as salicylic acid, benzoyl peroxide, adapalene, and tretinoin. Inflammatory acne is usually treated with topical therapy plus a systemic antibiotic. Nodulocystic acne generally requires an 8-week course of systemic antibiotics. If the nodulocystic acne does not improve, minocycline or isotretinoin may be needed. Topical therapy is often helpful in the long-term management of nodulocystic acne. New products are available that deliver topical agents in novel ways that decrease skin irritation. With the proper tools and instructions in use, most patients have significant improvement in their acne.

关键词：痤疮寻常/分类痤疮寻常/诊断痤疮寻常/药物疗法投药局部抗菌药/投药和剂量抗菌药/治疗应用皮肤科用药/投药和剂量诊断鉴别复方合剂药物疗法联合角质溶解药/投药和剂量维甲酸/投药和剂量人类

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Acne, perioral dermatitis, flushing, and rosacea: Unapproved treatments or indications

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CLINICS IN DERMATOLOGY 2000年第2期18卷 171-176页

作者： Katsambas, AD Nicolaidou, E Univ Athens Sch Med Dept Dermatol A Syggros Hosp Athens Greece

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Psoriasis, lichen planus, and disorders of keratinization: Unapproved treatments or indications

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CLINICS IN DERMATOLOGY 2000年第2期18卷 159-169页

作者： Capella, GL Finzi, AF Osped Maggiore IRCCS Dept Dermatol I-20122 Milan Italy

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Prevention of sodium lauryl sulfate irritant contact dermatitis by Pro-Q aerosol foam skin protectant

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JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY 1999年第5期40卷 783-785页

作者： Patterson, SE Williams, JV Marks, JG Penn State Univ Milton S Hershey Med Ctr Coll Med Dermatol Sect Hershey PA 17033 USA Ferndale Labs Ferndale MI 48220 USA

Eczematous skin disease is a serious work-related illness. Since 1995, reimbursement by insurance companies for treatment of skin diseases has become the largest cost source in some countries. This study was a randomized controlled trial (N = 20) of the efficacy of Pro-Q, a skin protectant product, in the prevention of contact dermatitis from sodium lauryl sulfate and urushiol, the resinous sap of poison ivy and poison oak. Pro-Q was significantly effective in reducing the irritation from sodium lauryl sulfate but did not prevent the allergic reaction to urushiol.

关键词：投药皮肤气雾剂儿茶酚类/副作用皮炎刺激性/预防和控制皮炎职业性/病因学皮炎职业性/预防和控制皮炎毒漆树/预防和控制皮肤科用药/投药和剂量皮肤科用药/治疗应用洗涤剂/副作用二甲基聚硅氧烷类双盲法湿疹/化学诱导湿疹/预防和控制甘油/投药和剂量甘油/治疗应用刺激剂/副作用植物有毒预防和防护用药/投药和剂量预防和防护用药/治疗应用二甲聚硅氧烷/投药和剂量二甲聚硅氧烷/治疗应用十二烷硫酸钠/副作用毒漆树人类

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Topical therapy for psoriasis with the use of augmented betamethasone and calcipotriene on alternate weeks

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JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY 2000年第1期43卷 61-65页

作者： Singh, S Reddy, DCS Pandey, SS Banaras Hindu Univ Dept Dermatol Inst Med Sci Varanasi 221005 Uttar Pradesh India Banaras Hindu Univ Dept Prevent Med Inst Med Sci Varanasi 221005 Uttar Pradesh India

Background: Topical corticosteroids, commonly used for psoriasis, show diminished response on continuous use. Objective: We tested efficacy of topical corticosteroid and calcipotriene used on alternate weeks versus daily corticosteroid in patients with psoriasis. Methods: In a randomized, observer-blind design, the experimental group of 25 patients with stable plaque psoriasis received augmented betamethasone dipropionate 0.05% cream once daily in the first and third weeks and calcipotriene 0.005% ointment twice daily in the second and fourth weeks. The control group of 27 patients received augmented betamethasone once daily for 4 weeks. Results: The experimental regimen was more effective than the control regimen as evidenced by (1) more patients with at least a 90% reduction in Psoriasis Area and Severity Index (PASI) score (difference 49.5%, 95% confidence interval [CI], 26.1%-72.9%, P<.001), (2) lower PASI after 2 weeks (P less than or equal to.04), and (3) greater percentage reduction in PASI after 2 and 4 weeks (difference 23.1% [CI, 11.1%-35.1%] and 46.4% [28.9%-63.8%], respectively;P<.001). The study had power of 93.7%. No patient had skin irritation. Conclusion: Use of augmented betamethasone and calcipotriene on alternate weeks is more effective than daily corticosteroid and represents a novel strategy for treating psoriasis.

关键词：投药局部消炎药/投药和剂量倍他米松/投药和剂量倍他米松/类似物和衍生物骨化三醇/投药和剂量骨化三醇/类似物和衍生物皮肤科用药/投药和剂量糖皮质激素类银屑病/药物疗法单盲法治疗结果成年人女(雌)性人类男(雄)性中年人

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Skin neoplasias including cutaneous lymphoma, melanoma, and others: Unapproved treatments or indications

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CLINICS IN DERMATOLOGY 2000年第2期18卷 201-210页

作者： Abel, EA Stanford Univ Sch Med Dept Dermatol Stanford CA 94305 USA

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Atopic dermatitis: Unapproved treatments or indications

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CLINICS IN DERMATOLOGY 2000年第2期18卷 153-158页

作者： Graham-Brown, R Leicester Royal Infirm Dept Dermatol Leicester LE1 5WW Leics England

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Dermatomyositis-like eruption and leg ulceration caused by hydroxyurea in a patient with psoriasis

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CLINICAL AND EXPERIMENTAL DERMATOLOGY 1999年第3期24卷 164-166页

作者： Varma, S Lanigan, SW Univ Wales Hosp Dept Dermatol Cardiff CF4 4XN S Glam Wales Princess Wales Hosp Dept Dermatol Bridgend Wales

We report the case of an elderly woman who had been on hydroxyurea for long-standing widespread psoriasis, After approximate to 5 years's treatment with hydroxyurea, she developed a symmetrical dermatomyositis-like eruption on her hands, together with bilateral leg ulceration. Although similar skin eruptions have been reported after long-term hydroxyurea treatment, all of the previous patients were being treated for myeloproliferative disorders. A dermatomyositis-like eruption has not previously been reported to occur as a consequence of hydroxyurea treatment for psoriasis. Its recognition is important to prevent unnecessary investigation or treatment withdrawal.

关键词：皮肤科用药/投药和剂量皮肤科用药/副作用皮肌炎/化学诱导药疹/病因学羟基脲/投药和剂量羟基脲/副作用腿溃疡/化学诱导核酸合成抑制剂/投药和剂量核酸合成抑制剂/副作用银屑病/药物疗法老年人老年人 80以上女(雌)性人类

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