Pharmacokinetics of dapsone gel, 5% for the treatment of acne vulgaris

BACKGROUND: Oral dapsone has been available for over 60 years and has been used to treat severe acne vulgaris; however, the oral formulation is known to cause dose-dependent haematological reactions and is currently indicated only for diseases such as dermatitis herpetiformis and Hansen's disease. A gel formulation of dapsone was recently developed to treat acne vulgaris. As dapsone is administered topically, it was expected that systemic absorption would be considerably lower than that observed with oral dapsone therapy, thereby avoiding any adverse haematological effects. OBJECTIVE: To report the pharmacokinetic profile of topically applied dapsone gel, 5% in the treatment of acne vulgaris. STUDY PARTICIPANTS AND METHODS: Three prospective, open-label studies enrolled a total of 548 subjects with acne vulgaris: two phase I pharmacokinetic studies (crossover and drug interaction) and one phase III long-term safety study. In the crossover study (n = 18), topical dapsone gel applied twice daily for a total of 14 days to 22.5% of the body surface area was compared with a single dose of oral dapsone 100mg (the typical clinical dose). In the drug-interaction study (n = 24), oral trimethoprim/sulfamethoxazole monotherapy, topical dapsone gel monotherapy and the two in combination were used twice daily for 7, 21 and 7 days, respectively. In the long-term safety study (n = 506), topical dapsone gel was applied twice daily to acne-affected areas for up to 12 months. Blood samples were drawn at various timepoints in each study to assess drug and metabolite concentrations. Systemic concentrations of dapsone, N-acetyl dapsone, dapsone hydroxylamine, trimethoprim and sulfamethoxazole were determined, according to the study design. RESULTS: In the crossover study, the mean area under the plasma concentration-time curve (AUC) from 0 to 24 hours for dapsone was 417.5 ng x h/mL after 2 weeks of dapsone gel therapy (n = 10), compared with an AUC from time zero to infinity of 52,641 ng x h/mL after a single dose of oral dapsone; this represents a 126-fold lower systemic exposure for dapsone gel at typical therapeutic doses. In the drug-interaction study, the AUC from 0 to 12 hours for dapsone was 221.52 ng x h/mL after 3 weeks of dapsone gel monotherapy compared with 320.3 ng x h/mL after 1 week of coadministration with trimethoprim/sulfamethoxazole. In the long-term safety study, the mean plasma dapsone concentrations ranged from 7.5 to 11 ng/mL over 12 months. Overall, total systemic exposures to dapsone and its metabolites were approximately 100-fold less for dapsone gel than for oral dapsone, even in the presence of trimethoprim/sulfamethoxazole. There were no reports of any haematological adverse events. CONCLUSIONS: Topical application of dapsone gel in various settings ranging from 2 weeks to 12 months resulted in systemic exposures to dapsone and its metabolites that were approximately 100-fold less than those after oral dapsone at a therapeutic dose level. The concentrations of dapsone and its metabolites reached steady state and did not increase during prolonged treatment.     

Clindamycin phosphate/tretinoin gel formulation in the treatment of acne vulgaris

Clindamycin phosphate 1.2% together with tretinoin 0.025% as a gel (CTG) is a topical formulation of a fixed and stable combination approved by the FDA for the treatment of acne vulgaris in patients 12 years of age or older. The main indication of CTG is the management of moderate comedonal and mild-to-moderate papulopustular acne, an acne form which is present in more than 50% of acne patients. CTG can also be combined with systemic antiacne therapy, such as systemic isotretinoin, in nodulocystic acne. The product combines the anti-inflammatory and antibacterial properties of clindamycin with the well proven and beneficial comedolytic and anticomedogenic effects of tretinoin (all-trans retinoic acid). The addition of clindamycin to tretinoin enhances the comedolytic efficacy of tretinoin in moderate-to-severe acne of the face. The comedolytic activity of tretinoin and the anti-inflammatory efficacy of clindamycin accelerate resolution of all types of acne lesions without affecting the safety of both compounds. Discontinuation rates due to adverse events related to this formulation were found to be low (≤ 1%). Safety of CTG use in pregnancy has not been established. The combination formulation is mainly designed to enhance effectiveness and minimize irritation. The once daily use of CTG, its rapid and dual effect and good tolerability have a positive impact on the duration of disease, patients' compliance and overall costs of therapy.     

Combination of azelaic acid 5% and clindamycin 2% for the treatment of acne vulgaris

Context and objective: Acne vulgaris, an inflammatory skin disease with different clinical appearances, is a common problem in most adolescents. It seems that using combinations of topical agents can decrease resistance to the treatment and improve the efficacy. Therefore, we evaluated the effects of azelaic acid (AA) 5% and clindamycin (Clin) 2% combination (AA-Clin) on mild-to-moderate acne vulgaris.

Materials and methods: The efficacy and safety of 12-week treatment with AA-Clin in patients with mild-to-moderate facial acne vulgaris were evaluated by a multicenter, randomized, and double-blind study. A total of 88 male and 62 female patients were randomly assigned to one of these treatments: AA 5%, Clin 2%, and combination of them. Every 4 weeks, total inflammatory and noninflammatory lesions were counted, acne severity index (ASI) was calculated, and patient satisfaction was recorded.

Results: Treatment for 12 weeks with combination gel significantly reduced the total lesion number compared with baseline (p?<?0.01), as well as Clin 2% or AA 5% treatment groups (p?<?0.05 or p?<?0.01). The percentage of reduction in ASI in combination treated group (64.16?±?6.01) was significantly more than those in the Clin 2% (47.73?±?6.62, p?<?0.05) and 5% AA (32.46?±?5.27, p?<?0.01) groups after 12 weeks. Among the patients in the AA-Clin group, 75.86% of males were satisfied or very satisfied and 85.71% of females were satisfied or very satisfied. This trend was significant in comparison to the number of patients who were satisfied with AA 5% or Clin 2% treatment (p?<?0.01). Seven patients in AA-Clin group (incidence?=?22%) showed adverse effects that were not statistically significant compared to treatment with individual active ingredients.

Discussion and conclusion: The profound reduction in lesion count and ASI by combination therapy with AA-Clin gel in comparison to individual treatment with 5% AA or Clin 2% suggested the combination formula as an effective alternative in treatment of acne vulgaris.     

阿达帕林凝胶治疗寻常痤疮临床观察

目的 :观察 0 1%阿达帕林凝胶治疗寻常痤疮的临床疗效和安全性。方法 :16 0例寻常痤疮患者 ,分别给予外涂 0 1%阿达帕林凝胶 (80例 )及 0 0 2 5 %全反维A酸凝胶 (80例 )。根据治疗前后炎性损害和非炎性损害总数减少的百分率评价疗效。结果 :两组痊愈率、显效率、有效率均无统计学差异 ,阿达帕林组不良反应率明显低于全反维A酸组。结论 :0 1%阿达帕林是一种局部治疗寻常痤疮的有效的安全的药物     

Tazarotene foam, 0.1%, for the treatment of acne

Introduction: Acne is a common skin condition of the pilosebaceous units that affects the young and old, ranges from moderate to severe and can be treated with an array of options. Topical retinoids are the initial treatment for acne due to their ability to treat comedones, the starting point of acne.

Areas covered: Tazarotene is a topical retinoid available as a cream, gel and foam. Tazarotene 0.1% foam was FDA approved in 2012 for the treatment of acne in patients ages ≥12 and is the first foam topical retinoid on the market. Phase I and III trials support the efficacy and safety of tazarotene foam for acne.

Expert opinion: The foam vehicles may increase compliance and satisfaction in some patients and as retinoids are commonly first line acne treatments, this new topical retinoid foam may be a useful option for some acne patients.     

Topical clindamycin in the management of acne vulgaris

A small cadre of antimicrobials are commonly used and regarded as effective and safe, as systemic and topical treatments of acne vulgaris. These include oral tetracycline, doxycycline, minocycline and topical clindamycin and erythromycin. Topical antimicrobials work via both antimicrobial and non-antimicrobial mechanisms: the former due to suppression of the growth of propionibacterial species (especially Propionibacterium acnes and P. granulosum). Clindamycin appears to be superior in efficacy compared with erythromycin and tetracycline. However, the emergence and spread of resistance among propionibacteria to both erythromycin and clindamycin calls into question their long-term viability as topical anti-acne therapies. Only through judicious use of combination topical therapies (e.g., topical retinoid, benzoyl peroxide or azelaic acid plus clindamycin or erythromycin) and the practice of effective infection control (i.e., handwashing between seeing patients in the clinic) can both clindamycin's and erythromycin's widespread utility be preserved in this disorder.     

克林霉素磷酸酯凝胶治疗痤疮

目的：观察克林霉素磷酸酯凝胶治疗痤疮的疗效。方法：痤疮１５４例随机分成３组,克林霉素磷酸酯凝胶１０４例,其中试验组５０例（男性１３例,女性 ３７例;年龄 ２３ ａ＋ ｓ ６ ａ）,开放组 ５４例（男性 １３例,女性 ４１例;年龄 ２４ ａ＋ ７ ａ）。磷酸克林霉素洗液５０例为对照组（男性 １８例,女性 ３２例;年龄２６ ａ±７ ａ）。上述药物每日早晚各 １次涂于患部,疗程均 ４ ｗｋ。结果： ３组治疗后炎性丘疹、脓疱改善较治疗前差异有显著意义（Ｐ＜０．０５或Ｐ＜０．０１）。试验组与对照组症状改善及疗效比较,差异无显著意义（Ｐ＞０．０５）。结论：克林霉素磷酸酯凝胶治疗痤疮疗效佳。     

五味消毒饮内服外敷治疗寻常性痤疮35例临床观察

目的:观察五味消毒饮加减内服外敷治疗寻常性痤疮临床疗效。方法:60例痤疮患者随机分为两组,治疗组35例,采用五味消毒饮加减内服外敷联合治疗方法。对照组25例,口服甲硝唑片,睡前外用维A酸乳膏。结果:治疗组痊愈率51.4%,总有效率97.1%;对照组痊愈率24.0%,总有效率80.0%。两组痊愈率与总有效率比较,差异均有显著性(P<0.05)。结论:五味消毒饮加减内服外敷法治疗寻常性痤疮有显著疗效,安全性好。     

复方克林霉素搽剂治疗寻常痤疮

目的 :观察复方克林霉素搽剂治疗寻常痤疮的疗效。方法 :采用开放、多中心临床试验方法以复方克林霉素搽剂治疗 153例寻常痤疮病人 (男性53例 ,女性 10 0例 ,年龄 2 2a±s 6a) ,每日 3次涂于面部 ,连续 4wk ,每 2wk随访。结果 :复方克林霉素搽剂治疗寻常痤疮 ,4wk总显效率达 83.0 % ,对脓疱和丘疹的总有效率分别为 96.1%和 80 .7% ,不良反应率为 1.9%。结论 :复方克林霉素搽剂治疗痤疮疗效显著 ,安全性高 ,使用方便     

阿达帕林凝胶治疗寻常性痤疮疗效及安全性研究

目的:通过阿达帕林凝胶与5%过氧苯甲酰霜对寻常性痤疮治疗的对照观察,评价阿达帕林凝胶治疗寻常性痤疮的疗效和安全性.方法:采用开放对照临床实验,分别应用阿达帕林凝胶与5%过氧苯甲酰霜对寻常性痤疮病人进行治疗,疗程12周,在治疗的2、4、8和12周进行随访.结果:阿达帕林凝胶治疗寻常性痤疮疗效和安全性均高于5%过氧苯甲酰霜剂.结论:阿达帕林凝胶是治疗寻常性痤疮安全和有效的药物.     

他扎罗汀乳膏与阿达帕林凝胶随机对照治疗寻常型痤疮多中心临床试验

目的 评价国产0．1％他扎罗汀乳膏治疗面部轻中度寻常型痤疮的疗效及安全性。方法 用多中心、随机单盲对照试验方法，0．1％他扎罗汀乳膏或0．1％阿达帕林凝胶局部外用每日1次，疗程8周。在治疗前、治疗2，4和8周进行观察。入选病例142例，其中0．1％他扎罗汀乳膏组71例，完成8周观察64例。0．1％阿达帕林凝胶组71例，完成8周观察67例。结果他扎罗汀乳膏组有效率72．3％，阿达帕林凝胶组有效率62．7％。两组之间无显著统计学差异。两组的不良反应均表现为轻度到中度的局部刺激，发生率分别为28．70％和23．50％。结论 他扎罗汀乳膏治疗寻常型痤疮安全有效。     

异维A酸凝胶治疗寻常痤疮多中心随机双盲安慰剂对照临床研究

目的 评价0.05%异维A酸凝胶（抗面部痤疮药）治疗寻常痤疮的疗效及安全性.方法 用多中心随机双盲安慰剂对照试验设计,以凝胶基质为对照,2药分别外用患处,每日2次,疗程12周.结果 0.05%异维A酸凝胶与凝胶基质比较,治疗寻常痤疮的有效率分别为78.5%和23.3%;2药的药物不良反应发生率分别为23.2%和15.6%（P＞0.05）.结论 0.05%异维A酸凝胶治疗寻常痤疮是安全有效的外用药物.     

异维A酸治疗重度痤疮的疗效观察

唐志凌 天津市蓟县人民医院皮肤科（301900） 【摘要】 目的 观察异维A酸治疗重度痤疮的疗效。方法 将受试者随机分为两组,试验组中体重≥50kg者,隔日口服异维A酸10mg,每日3次;体重<50 kg者,隔日口服异维A酸10mg,每日2次。对照组:盐酸米诺环素50mg每日2次。两组患者疗程均为8周。治疗第1、2、4、6、8周及停药后2、4、6周,分别对两组患者有效率进行评分比较。结果 在治疗第2、4、6、8周,试验组与对照组比较,有效率均差异显著。在停药后2、4、6周,试验组和与对照组比较,有效率仍有显著差异。结论 异维A酸治疗重度痤疮的疗效优于米诺环素。     

红霉素醋酸锌凝胶和软膏治疗寻常型痤疮

目的：评价红霉素醋酸锌凝胶和软膏治疗寻常型痤疮的疗效和安全性。方法：采用随机、双盲、平行对照试验。以1%克林霉素磷酸酯凝胶为对照,设红霉素醋酸锌凝胶和红霉素醋酸锌软膏2个试验组,用药后6 wk评价疗效,并观察不良反应。结果：共入选60例病人。58例完成试验,对照组、软膏组和凝胶组各有19例,20例和19例。治疗6 wk后3组病人的黑头粉刺、白头粉刺、炎性丘疹和脓疱数较治疗前均有显著下降(P＜0.01),3组间变化无差异(P＞0.05)。对照组、软膏组和凝胶组有效率分别为58%,65%和63%,各组间疗效比较差异无显著意义(P＞0.05)。3组皮肤局部不良反应发生分别为3例,1例和1例,无全身不良反应发生。结论：红霉素醋酸锌凝胶和软膏是安全有效的治疗寻常型痤疮的外用药。     

Versatility of azelaic acid 15% gel in treatment of inflammatory acne vulgaris

Azelaic acid (AzA) 15% gel is approved for the treatment of rosacea in the US, but also has approval for the treatment of acne vulgaris in many European countries where it has demonstrated success. Two randomized, multicenter, controlled clinical trials compared the effects of AzA 15% gel with those of topical benzoyl peroxide 5% or topical clindamycin 1%, all using a twice-daily dosing regimen. The primary endpoint in the intent-to-treat analysis was a reduction in inflammatory papules and pustules. AzA 15% gel resulted in a 70% to 71% median reduction of facial papules and pustules compared with a 77% reduction with benzoyl peroxide 5% gel and a 63% reduction with clindamycin. AzA 15% gel was well-tolerated. In addition, a 1-year European observational study conducted by dermatologists in private practice evaluated the safety and efficacy of AzA 15% gel used as monotherapy or in combination with other agents in more than 1200 patients with acne. Most physicians (81.9%) described an improvement in patients' symptoms after an average of 34.6 days, and 93.9% of physicians reported patient improvement after an average of 73.1 days. Both physicians and patients assessed AzA 15% gel to be effective with 74% of patients being "very satisfied" at the end of therapy. AzA 15% gel was considered "well-tolerated" or "very well-tolerated" by 95.7% of patients. The majority of patients were more satisfied with AzA than with previous therapies. AzA 15% gel represents a new therapeutic option for the treatment of acne vulgaris.     

Evaluating FMX-101 as a promising therapeutic for the treatment of acne

ABSTRACT

Introduction

Oral minocycline is a mainstay of therapy for moderate-to-severe acne; however, systemic side effects which include hepatotoxicity, lupus-like syndrome, drug hypersensitivity syndrome, autoimmune hepatitis, polyarteritis nodosa, gastrointestinal side effects and skin hyperpigmentation are of concern. Topical antibiotics commonly used in acne, such as erythromycin and clindamycin, present high P. acnes resistance rates which has opened the market for new topical antibiotics. FMX-101 is a novel topical minocycline foam that has shown promising results in phase I, II and III trials for the treatment of moderate-to-severe acne with a better safety profile than oral minocycline.     

异维A酸胶丸治疗结节囊肿性痤疮196例的疗效

目的：观察异维A酸胶丸治疗结节囊肿性痤疮的临床疗效。方法：选择门诊痤疮患者326例进行治疗,随机分成试验组和对照组。试验组196例,口服异维A酸胶丸,剂量0.4mg.kg^-1.d^-1,bid;对照组130例,口服红霉素12mg.kg^-1.d^-1,bid。两组均给药12周后观察疗效。结果：试验组有效率显著高于对照组（73.47%vs48.46%,P〈0.05）。两组均无明显不良反应发生。结论：异维A酸胶丸治疗结节囊肿性痤疮疗效确切。     

异维A酸红霉素凝胶治疗寻常痤疮的多中心随机平行对照临床试验

目的:评价异维A酸红霉素凝胶治疗轻、中度寻常痤疮的疗效和安全性。方法:采用多中心随机、盲法、阳性药平行对照试验设计。试验组予异维A酸红霉素凝胶,对照组予维A酸乳膏。均为每晚一次,涂抹在全部患处,疗程为8 wk,观察疗效及不良反应。结果:共入组240例病人,进入疗效分析226例,其中试验组111例,对照组115例。治疗后,试验组与对照组综合疗效有效率分别为87.4% (97/111)和81.7%(70/115),2组综合疗效无显著差异(P>0.05);不良反应发生率分别为10.2%和7.6%(P>0.05)。结论:异维A酸红霉素凝胶治疗轻、中度寻常痤疮安全有效。     

维胺酯2种给药方案治疗寻常痤疮44例

目的 :观察维胺酯不同剂量治疗痤疮的疗效和安全性 ,探索有效治疗方案。方法 :将 4 4例中、重度寻常痤疮病人分为 2组 ,A组 2 4例 ,总疗程 6mo ,分别在mo 1～ 2按 1mg·kg- 1·d- 1;在mo 3～ 4按 2 5mg ,qd ;在mo 5～ 6按 2 5mg ,qod的剂量口服。B组 2 0例 ,5 0mg ,tid ,总疗程 6wk。结果 :2组总累积量A组为 (6 14 3±s 5 71)mg ,B组为 6 30 0mg ;治疗后临床评分分别为 (7.7± 1.7)分vs(7.7±1.6 )分 ;基本痊愈率分别为 5 4%vs 5 0 % ,差异均无显著意义 (P >0 .0 5 )。日剂量分别为 (0 .5 3±0 .0 3)mg·kg- 1·d- 1vs (2 .4± 0 .3)mg·kg- 1·d- 1、不良反应率为 8%vs 4 0 % ;复发率 12 %vs4 5 % ,差异均有显著意义 (P <0 .0 5或P <0 .0 1)。结论 :应用维胺酯低剂量长疗程治疗寻常痤疮 ,疗效好 ,安全性高 ,复发率低。     

百癣夏塔热片联合夫西地酸乳膏治疗寻常痤疮的临床研究

目的探讨百癣夏塔热片联合夫西地酸乳膏治疗寻常痤疮的临床疗效。方法选取2017年6月—2018年6月在监利县人民医院治疗的寻常痤疮患者98例,根据用药的不同分为对照组(49例)和治疗组(49例)。对照组患者取适量夫西地酸乳膏涂于患处,3次/d;治疗组在对照组基础上口服百癣夏塔热片,1.55 g/次,3次/d。两组患者均治疗4周。观察两组患者临床疗效,同时比较治疗前后两组患者红斑、色素沉着、Acne-QOL和SF-36评分及血清白细胞介素-8(IL-8)、可溶性白细胞介素-2受体(sIL-2R)、肿瘤坏死因子-α(TNF-α)、IL-10和γ干扰素(IFN-γ)水平。结果治疗后,对照组临床有效率为81.63%,显著低于治疗组的97.96%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者红斑、色素沉着评分显著降低(P0.05),Acne-QOL和SF-36评分显著升高(P0.05),且治疗组红斑、色素沉着、Acne-QOL和SF-36评分明显优于对照组(P0.05)。治疗后,两组患者血清IL-8、s IL-2R和TNF-α水平均显著降低(P0.05),IL-10和IFN-γ水平显著升高(P0.05),且治疗组上述炎症因子水平明显好于对照组(P0.05)。结论百癣夏塔热片联合夫西地酸乳膏治疗寻常痤疮可有效改善患者临床症状,促进皮损修复,降低机体炎症反应,提高患者生活质量。