萘替芬酮康唑乳膏治疗体股癣和手足癣200例的疗效观察

目的:探讨萘替芬酮康唑乳膏治疗体股癣和手足癣的临床效果。方法:选择我院体股癣和手足癣患者共200例,上述患者分为两组,观察组和对照组。观察组给予萘替芬酮康唑乳膏治疗,对照组给予达克宁霜治疗。评定两组治疗效果。结果:观察组治疗后有效率为95.0%(95/100)。对照组治疗后有效率为84.0%(84/100)。结论:萘替芬酮康唑乳膏治疗体股癣和手足癣疗效显著,安全且副作用少。     

Adapalene gel 0.1% vs ketoconazole cream 2% and their combination in treatment of pityriasis versicolor: A randomized clinical study

Pityriasis versicolor (PV) is a chronic superficial fungal infection. Management using azole drugs leads to drug resistance. The present study aimed to compare the clinical outcome of 0.1% adapalene gel vs 2% ketoconazole cream and their combination in PV. This randomized double‐blinded study was conducted on 90 PV patients divided into three equal groups. GI was treated with topical ketoconazole 2% cream twice daily and placebo, GII was treated with topical 0.1% adapalene gel twice daily and placebo and GIII was treated with topical combination of 0.1% adapalene gel (at night) and ketoconazole 2% cream (in the morning). All patients received medications for 4 weeks. Evaluation was done at 2 and 4 weeks and included clinical assessment, laboratory assessment, and patient satisfaction. We found that after 4 weeks of treatment, all groups showed significant improvement. There was better response in GIII in terms of lower rate of positive potassium hydroxide staining, higher rate of significantly improved cases and higher rate of well‐satisfied patients. However, the difference fell short of statistical significance. We concluded that a combination of adapalene gel and ketoconazole cream is very effective in treatment of PV with no or mild side effects.     

白藜芦醇通过拮抗hPXR对P-gp的影响

目的研究白藜芦醇通过拮抗hPXR对P-gp基因(MDR1)、蛋白表达及活性的影响。方法在LS174T细胞中,采用瞬时共转染报告基因实验研究白藜芦醇对PXR介导的MDR1的转录调节作用,并进一步应用Real-Time定量PCR和Western blot方法检测白藜芦醇作用24 h后对利福平诱导的P-gp基因和蛋白变化的影响,罗丹明转运实验考察P-gp活性的变化。结果双荧光素酶报告基因检测结果显示,25和50μmol.L-1白藜芦醇可通过拮抗PXR将利福平对MDR1的诱导作用由4.70倍分别降至1.76倍和0.69倍(P<0.01),在过表达hPXR的LS174T细胞中,50μmol.L-1白藜芦醇可以将利福平诱导的MDR1 mRNA水平由1.8倍降至1.3倍(P<0.05),Western blot结果表明白藜芦醇也可降低利福平诱导的P-gp表达。此外,罗丹明转运实验显示,25和50μmol.L-1白藜芦醇可以将利福平抑制的累积量由77.7%升至91.7%和95.1%(P<0.05),表明白藜芦醇可降低利福平诱导的P-gp活性。结论白藜芦醇可以通过拮抗PXR而影响P-gp的基因、蛋白表达及活性。     

双戊烯对酮康唑透皮吸收促进作用

目的：研究双戊烯的透皮促进作用。方法：采用自制透皮扩散装置。以离体小白鼠背部皮肤为透皮屏障，紫外分光光度法测定含不同浓度双戊烯和氮酮对酮康唑的促透效果。结果：不同浓度促进剂对酮康唑的促透效果顺序为3％双戊烯＞2％双戊烯＞3％氮酮＞1％双戊烯。结论：实验证明，3％双戊烯对酮康唑具有较好的促透作用，与其它浓度的双戊烯和不同浓度的氮酮相比具有显著性差异（P＜0．05）或极显著性差异（P＜0．01）。     

Antimikrobielle Effekte des in vitro simulierten Ketoconazol-Kantharidinblasenflüssigkeitsspiegel-Profils bei Candida albicans*,**/Antimicrobial Effects of Ketoconazole Concentration Profiles in Cantharidin Blister Fluid,Simulated in Vitro,on Candida albicans

Zusammenfassung: Candida albicans (Isolat Nr. 5125/85) wurde zum einen in Sabouraud-Glukose-Bouillon, zum anderen in einem flüssigen synthetischen Aminosäuremedium gegenüber ständig schwankenden Konzentrationen von Ketoconazol exponiert. Zugrundegelegt wurden die Profile der freien wie die der Gesamtkonzentrationen, die beim Menschen nach einmaliger oraler Gabe von 200 mg in kutaner Kantharidinblasenflüssigkeit gefunden wurden. Parallel zu jedem Versuchsansatz mit Ketoconazol wurde jeweils ein Ansatz ohne Wirkstoff mitgeführt. Bei Verwendung des ersteren, die Hefeform begünstigenden Mediums fand sich nur eine relativ geringe Wachstumshemmung. In dem die Pseudomyzelform begünstigenden synthetischen Medium war demgegenüber — konzentrationsabhängig — ein deutlicher antimikrobieller Effekt zu erkennen (Keimdichtenzunahme in Gegenwart der Gesamtkonzentration auf das 2, lfache, im Kontrollversuch auf das 15, 3fache). Die größere Wirksamkeit von Ketoconazol auf die Pseudomyzelform von Candida albicans wird wiederum bestätigt, zugleich wird die geringere Sicherheitsmarge bei der systemischen Behandlung mit Azolen gegenüber der antimikrobiellen Chemotherapie mit Antibiotika deutlich. Untersuchungen vom vorliegenden Typ — wie sie in der klinischen Bakteriologie schon öfter durchgeführt wurden — könnten auch bei der Untersuchung neuer Antimykotika zunehmend an Bedeutung gewinnen. Summary: Candida albicans was exposed to continously changing concentrations of Ketoconazole in, on the one hand, Sabouraud Dextrose Broth and, on the other hand, a liquid synthetic amino-acid medium. The profiles of the free and total concentrations found in cutaneous cantha-ridin blister-fluid in humans after a single oral dose of 200 mg were used as basic information. For every experiment with ketoconazole, an identical experiment without addition of an antimycotic was carried out Using the first, yeast-promoting medium, only a relatively small growth-inhibition was evident. Using the synthetic amino-acid medium, which promotes the pseudomycelial form, however, a marked, concentration-dependent, antimicrobial effect was observed. (The colonial density of Candida albicans increased 2.1 times in the presence of the total ketoconazole concentrations, compared with 153 times in the control experiment.) The greater effectiveness of ketoconazole against the pseudomycelial form of Candida albicans is again confirmed. At the same time, the smaller safety margin associated with systemic treatment with azoles as compared with anti-microbial therapy with antibiotics, is apparent. Investigations of the present type, which have often been carried out in clinical bacteriology, may also gain significance in the investigation of new antimycotics.     

二阶导数分光光度法测定复方酮康唑软膏中酮康唑含量

本文采用二阶导数分光光度法直接测定酮康唑的含量。实验结果表明：本法简便、正确、重现性好。在16～48μ/ml浓度范围内线性良好。r=0．9994，RSD=0．65％。     

The prognostic factors of effective ketoconazole treatment for metastatic castration-resistant prostate cancer: who can benefit from ketoconazole therapy?

We investigated the prognostic value of some variables of effective ketoconazole treatment for metastatic castration-resistant prostate cancer (mCRPC). In total, 163 patients with mCRPC were eligible, receiving ketoconazole 200–400 mg three times daily with replacement doses of prednisone. Progression-free survival (PFS) was calculated from the beginning of the ketoconazole therapy to the onset of disease progression. The prognostic value of different variables for PFS was assessed by Cox regression analysis. The median PFS was 2.6 months (0.5–8.6 months) for these patients. The serum testosterone level changed during therapy, which decreased when the prostate-specific antigen (PSA) declined; the serum testosterone level increased as the levels of PSA relapsed. The median PFS values for patients associated with different factors were the following: 1.4 and 3.5 months for a nadir PSA of ≥0.2 and <0.2 ng ml⁻¹, respectively (hazard rate (HR)=4.767, P<0.001); 3.1 and 1.6 months for a baseline testosterone of ≥0.1 and <0.1 ng ml⁻¹, respectively (HR=2.865, P=0.012); 2.8 and 1.9 months for a baseline haemoglobin of ≥120 and <120 g l⁻¹, respectively (HR=1.605, P<0.001); and 3.0 and 1.9 months for a PSA doubling time (PSADT) of ≥2.0 and <2.0 months, respectively (HR=1.454, P=0.017). A risk model was constructed according to the four factors that divided patients into three subgroups of low risk (0–1 factors), moderate risk (2 factors) and high risk (3–4 factors) with PFS values of 3.6, 3.0 and 1.4 months, respectively (HR=1.619, P<0.001). A nadir PSA of ≥0.2 ng ml⁻¹, a baseline testosterone of <0.1 ng ml⁻¹, a baseline haemoglobin of <120 g l⁻¹ and a PSADT of <2 months were associated with a poor PFS. This risk model could provide evidence to predict the survival benefit of ketoconazole therapy.     

Effects of Ketoconazole on the Pharmacokinetic Properties of CG100649, A Novel NSAID: A Randomized,Open-Label Crossover Study in Healthy Korean Male Volunteers

Background

CG100649, a novel selective cyclooxygenase-2 inhibitor that also inhibits carbonic anhydrase I/II, is expected to reduce the cardiovascular risk typical of other NSAIDs. Concurrent medications may influence the activities of the cytochrome P450 (CYP) 3A enzyme through which CG100649 is metabolized.

Objectives

This study was designed to evaluate the influence of ketoconazole, a known strong inhibitor of CYP3A, on the pharmacokinetic properties of CG100649.

Methods

This randomized, open-label, 2 × 2 crossover study was conducted in healthy Korean male volunteers. Each subject received the following 2 treatments in a randomly allocated sequence, separated by a washout period of 42 days: single oral dose of CG100649 6 mg, and concurrent dosing of CG100649 6 mg and ketoconazole 400 mg followed by ketoconazole 400 mg/d over 4 days. Blood samples for pharmacokinetic analysis were collected at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 240, 384, and 480 hours after dosing of CG100649 in each sequence. Tolerability assessments were performed throughout the study.

Results

Thirty subjects participated, and 26 subjects completed the study. Seventeen adverse events (AEs) were reported in 10 subjects, and all AEs were recovered without any sequelae. No serious AEs were reported. Six subjects receiving the single dose of CG100649 had 9 AEs, and 7 subjects receiving the combination of ketoconazole and CG100649 had 8 AEs. The C_max of CG100649 with CG100649 only and with concurrent administration of CG100649 + ketoconazole were similar (10.7 and 11.0 ng/mL, respectively). The CG100649 AUC_last with concurrent ketoconazole was 1.29-fold greater than that with CG100649 only (2074.0 and 2685.8 ng · h/mL) and demonstrated a statistically significant difference (P < 0.05). However, there were no statistically significant differences in vital signs, clinical laboratory test results, ECGs, or AEs between treatments.

Conclusion

Although the AUC of CG100649 increased by 29% with the concurrent medication of ketoconazole, it is considered that concurrent administration of CG100649 with ketoconazole would not change the safety profile of CG100649. ClinicalTrials.gov identifier: NCT01154764.