Ketoconazole enantiomer for the treatment of diabetes mellitus

The impact of hypercortisolism on multiple metabolic conditions is well recognized; the metabolic manifestations of Cushing's syndrome overlap with those seen in type 2 diabetes and the metabolic syndrome. Ketoconazole (KTZ), a widely used antifungal agent that inhibits various enzymes in adrenal cortisol synthesis, is effective in treating hypercortisolemia, but its use is limited by toxicities. KTZ is a racemic compound of two cis-enantiomers: (2R,4S)-(+)-KTZ and (2S,4R)-(-)-KTZ. The consideration of an enantiomer with selective effect but minimal metabolic toxicity has driven the development of DIO-902 ([2S,4R]-[-]-KTZ) for the treatment of patients with type 2 diabetes and the metabolic syndrome. To evaluate the safety profile and effect of KTZ enantiomer, (2S,4R)-(-)-KTZ, on cortisol production, glycemia, and lipid profiles in patients with type 2 diabetes. Review of multiple published studies and examination of preliminary results from a Phase IIb clinical trial. Twelve weeks of treatment with DIO-902 resulted in reduced levels of HbA1c, FPG, total and LDL cholesterol as well as weight loss and decreased BP. In a previously conducted Phase IIa study, C-reactive protein levels decreased with DIO-902 treatment. Unfortunately, the development of this agent has been terminated due to unacceptable safety profiles.     

Concomitant administration of cyclosporine and ketoconazole in idiopathic nephrotic syndrome.

BACKGROUND: The deliberate use of ketoconazole to reduce the need for cyclosporine (CsA) is not new, but it is particularly relevant because of the high cost of CsA. Many studies have documented this benefit in renal and cardiac transplants, but this co-administration has not been reported in patients with nephrotic syndrome. METHODS: This retrospective study included 207 nephrotic patients who were steroid resistant, dependent or frequent relapsers and received CsA therapy. Among these patients 153 received daily ketoconazole therapy in a dose of 50 mg with concomitant decrease of one-third of the CsA dose while 54 patients received CsA alone. The majority of our cases were children (179 were below 18 years) and male to female ratio was 1.7:1. RESULTS: The great majority of the study population received the drugs for 1-2 years. Patients who received CsA and ketoconazole were comparable with those who received CsA alone regarding age, sex, duration of renal disease, renal pathology, severity of nephrotic syndrome, renal function, hepatic function and steroid response. Co-administration of ketoconazole significantly reduced mean doses of CsA by 37% after 1 month and 47% at 1 year with overall net cost savings of 37%. Hepatic functions remained within the normal range in both groups. Additionally, co-administration of ketoconazole significantly improved the response to CsA therapy, successful steroid withdrawal and decreased the frequency of renal impairment. CONCLUSIONS: Co-administration of keto with CsA in idiopathic nephrotic patients significantly reduces CsA costs and may improve its response.     

丹参酮联合酮康唑治疗头皮脂溢性皮炎疗效观察

目的:评价丹参酮联合酮康唑治疗头皮脂溢性皮炎的疗效。方法:86例头皮脂溢性皮炎患者,随机分成2组。治疗组47例口服丹参酮加外用酮康唑,对照组39例口服复合维生素B加外用酮康唑,4周末观察疗效。结果:治疗组和对照组痊愈率分别为74.5%、53.8%(P0.05),有效率分别为100%、82.1%(P0.05)。结论:丹参酮联合酮康唑治疗头皮脂溢性皮炎疗效好,安全性高。     

臭氧水联合臭氧油治疗足癣的疗效

目的：观察臭氧水联合臭氧油治疗足癣的临床疗效和不良反应。方法：60例确诊为足癣的患者随机被分 为对照组和臭氧组。对照组患者足癣用自来水清洗后用萘替芬酮康唑软膏外涂,每日1次;臭氧组患者足癣用臭氧水 清洗后外涂臭氧油,每日1次;均治疗4周。在治疗第1,2和4周结束时,分别采集临床评分数据评价患者病情的改善 情况;并在治疗前、治疗第4周末进行真菌镜检,评估真菌感染的情况。结果：治疗4周后,真菌镜检结果显示臭氧 组1例阳性,对照组6例阳性,两组间真菌镜检阳性率比较差异无统计学意义(P>0.05)。第1,2,4周的临床评分比较 显示不同时间点两组治疗效果差异无统计学意义(P>0.05)。结论：臭氧水联合臭氧油外用治疗足癣有效,且无不良 反应。     

特比萘芬与萘替芬酮康唑联合治疗外耳道真菌病的疗效分析

目的观察口服特比萘芬联合外用萘替芬酮康唑治疗外耳道真菌病的疗效、安全性。方法将66例外耳道真菌病患者随机分为两组：治疗组34例,口服特比萘芬联合外用萘替芬酮康唑,疗程1月;对照组32例,局部外用萘替芬酮康唑,疗程1月。结果治疗组1月后有效率为94.1%,高于对照组的53.1%,有显著性差异。结论联合疗法和单一外用药物治疗外耳道真菌病均有效,但联合疗法起效快、疗程短、效果好。     

新型酮康唑喷膜的制备及其对湿疹和体癣豚鼠模型的疗效

目的:制备新型酮康唑缓释喷膜,观察其对湿疹和体癣豚鼠模型的疗效.方法:以壳聚糖盐酸盐为成膜辅料,研制新型酮康唑喷膜,采用HPLC法测定其含量.色谱条件:Waters Symttry C18色谱柱(250 mm×4.6 mm,5 μm);流动相为甲醇-磷酸二氢钾缓冲液(4∶1);流速为0.6 ml/min;检测波长为239 nm;柱温为(22±2)℃.建立新型酮康唑喷膜的质量控制标准.观察新型酮康唑喷膜对豚鼠湿疹和体癣模型的疗效,以喷膜基质作对照,并分别与地塞米松止痒霜和复方酮康唑霜的疗效相比较.结果:酮康唑和醋酸地塞米松的线性范围分别为0.2～2.0 mg/ml和0.02～0.20 mg/ml;回收率分别为98.41%和97.84%;两者日内RSD和日间RSD分别为1.17%和1.26%、1.57%和1.40%.皮肤刺激性实验表明其对豚鼠皮肤无刺激.新型酮康唑喷膜对湿疹和体癣模型疗效分别与地塞米松止痒霜和复方酮康唑霜相当.结论:新型酮康唑喷膜制备工艺简单,对湿疹和体癣模型疗效确切,具备复方制剂的优势.     

胶束电动毛细管色谱法测定复方酮康唑霜中酮康唑和特美呋的含量

目的:毛细管电泳法测定酮康唑霜中酮康唑和特美味的含量。方法:分离缓冲液为胆汁酸钠(70 mmol/L)-三羟甲基氨基甲烷-磷酸(50 mmol/L)(pH 8.14),分离电压30 kV、温度25 C、50 μm(内径)×48.5cm(有效长度40cm)空心熔融石英毛细管柱、检测波长240nm。结果:以丙酸睾酮为内标,酮康唑质量浓度在140.5～702.5 μg/ml、特美呋质量浓度在151～755μg/ml之间成良好的线性关系;加样回收率分别为95.4％～103.9％、95.9％～102.6％,RSD％分别为2.8％～4.2％(n=3)、2.9％～3.6％。结论:本法简便、快速、可靠,可用于该复方制剂中酮康唑及特美呋的含量测定。