Recommendations for the treatment of fungal pneumonias

Incidences of fungal pneumonias have increased in immunocompromised patients with HIV infection or receiving bone marrow replacement or solid organ transplantation. Fungal pneumonias including aspergillosis, cryptococcosis, candidiasis, coccidioidomycosis, histoplasmosis and blastomycosis are one of the major causes of morbidity and mortality among the immunosuppressed hosts. Therefore, clinicians should consider the most appropriate and aggressive treatment of fungal pneumonias in this population. This report outlines the state of the art in the treatment of fungal pneumonias and discusses recent advances in antifungal therapy. Practice guidelines for the treatment with commonly used antifungal agents including amphotericin B, fluconazole, itraconazole, ketoconazole and flucytosine, are very useful for clinicians to manage the diseases appropriately. Echinocandins and second-generation triazoles will hopefully help clinicians to overcome the limitations of the current therapy.     

Pharmacotherapy of onychomycosis

Fungal infections of the nails are frequent in some segments of the population. Dermatophytes, yeasts and moulds are potential pathogens. A series of antifungal treatments are available to the clinician, differing by both their mechanistic nature and mode of administration. The pharmacodynamic and pharmacokinetic properties of each antifungal agent are distinct. This review focuses on the characteristics of amorolfine, bifonazole, ciclopirox, fluconazole, griseofulvin, itraconazole, ketoconazole, ravuconazole, R126638 and terbinafine. Single drug treatments and combined therapies are presented. None of the current drug regimens have demonstrated reliable efficacy against all cases of onycho-mycosis. Treatment failures, relapses and reinf-ections remain stubborn pro-blems in the management of onychomycosis.     

伊曲康唑在侵袭性真菌感染中的预防作用

由于免疫抑制剂的使用、血液系统恶性肿瘤病人异基因造血干细胞移植等高危人群的不断增多,侵袭性真菌感染的患病率和病死率均呈显著上升趋势。近年来伊曲康唑口服液和注射液相继在欧美及我国批准使用,对于高危病人伊曲康唑的预防性应用能显著降低侵袭性真菌感染的发生率。因此,本文拟从循证医学的角度,对伊曲康唑口服液和注射液在各种危重病病人侵袭性真菌感染中的预防作用作一综述。     

Factors influencing the magnitude and clinical significance of drug interactions between azole antifungals and select immunosuppressants

The magnitude of drug interactions between azole antifungals and immunosuppressants is drug and patient specific and depends on the potency of the azole inhibitor involved, the resulting plasma concentrations of each drug, the drug formulation, and interpatient variability. Many factors contribute to variability in the magnitude and clinical significance of drug interactions between an immunosuppressant such as cyclosporine, tacrolimus, or sirolimus and an antifungal agent such as ketoconazole, fluconazole, itraconazole, voriconazole, or posaconazole. By bringing similarities and differences among these agents and their potential interactions to clinicians' attention, they can appreciate and apply these findings in a individualized patient approach rather than follow only the one-size-fits-all dosing recommendations suggested in many tertiary references. Differences in metabolism and in the inhibitory potency of cytochrome P450 3A4 and P-glycoprotein influence the onset, magnitude, and resolution of drug interactions and their potential effect on clinical outcomes. Important issues are the route of administration and the decision to preemptively adjust dosages versus intensive monitoring with subsequent dosage adjustments. We provide recommendations for the concomitant use of these agents, including suggestions regarding contraindicated combinations, those best avoided, and those requiring close monitoring of drug dosages and plasma concentrations.     

伊曲康唑分散片在健康人体的生物等效性

目的研究伊曲康唑分散片和伊曲康唑胶囊(抗真菌药)在健康人体的生物等效性。方法采用两制剂双周期双交叉随机自身对照试验设计,20名男性健康志愿者分别口服伊曲康唑胶囊0.2g和伊曲康唑分散片0.2g(参比制剂和受试制剂),用HPLC法测定给药后不同时刻伊曲康唑的血药浓度,用DASVer1.0计算药代动力学参数。结果受试制剂与参比制剂的伊曲康唑主要药代动力学参数:t1/2分别为(20.89±4.58)、(21.05±4.37)h,Cmax分别为(244.3±69.8)、(240.2±66.3)ng·mL-1,tmax分别为(4.05±0.91)、(3.98±1.12)h,AUC0-72分别为(2786.5±670.3)、(2802.8±612.3)ng·h·mL-1,受试制剂与参比制剂相比平均相对生物利用度为(96.8±8.7)%。结论2种制剂在人体内具有生物等效性。     

氟康唑和伊曲康唑先后应用致麻疹样疹

1例78岁女性患者因脑出血、右侧中枢性偏瘫、肺部感染住院治疗。入院第21天，尿、便中检出霉菌孢子和菌丝，考虑霉菌感染。给予氟康唑静脉滴注治疗，首日0．4g／d，以后0．2g／d。3d后患者胸腹部出现红色斑疹，轻度瘙痒。停用氟康唑，改用伊曲康唑0．25g，2：L／d静脉滴注。治疗2d后，患者躯干和四肢红色斑疹继续增多，瘙痒显著。停用伊曲康唑，改用大蒜素静脉滴注并口服氯苯那敏抗过敏治疗，5d后皮疹基本消退。     

临床药师参与2例肺曲霉菌感染合理用药病例报道

本文报道临床药师参与2例肺曲霉菌感染合理应用抗真菌治疗方案制定,取得良好疗效,避免了药物不良反应。临床药师深入临床一线,提供药学服务有助于提高疗效,减少不良反应。     

Exploring the feasibility of the use of biopolymers as a carrier in the formulation of amorphous solid dispersions – Part I: Gelatin

Biopolymers have rarely been used so far as carriers in the formulation of amorphous solid dispersions (ASD) to overcome poor solubility of active pharmaceutical ingredients (APIs). In an attempt to enlarge our knowledge on this topic, gelatin, type 50PS was selected. A screening study was initiated in which twelve structurally different poorly soluble biopharmaceutical classification system (BCS) Class II drugs (carbamazepine, cinnarizine, diazepam, itraconazole, nifedipine, indomethacin, darunavir (ethanolate), ritonavir, fenofibrate, griseofulvin, ketoconazole and naproxen) were selected for evaluation. Solid dispersions of five different drug loadings of these twelve compounds were prepared by lyophilization and evaluated for their solid state properties by mDSC and XR(P)D, and in vitro dissolution performance. Even without any process optimization it was possible to form either fully amorphous or partially amorphous systems, depending on the API and API to carrier ratio. Hence in this respect, gelatin 50PS behaves as any other carrier. Dissolution of the API from the solid dispersions significantly exceeded that of their crystalline counterparts. This study shows the potential of gelatin as a carrier to formulate amorphous solid dispersions.     

口服伊曲康唑与外用酮康唑洗剂联合治疗糠秕孢子菌性毛囊炎

目的:观察口服伊曲康唑与外用酮康唑洗剂联合治疗糠秕孢子菌性毛囊炎的疗效。方法:选择临床症状典型,经真菌学检查确诊的糠秕孢子菌性毛囊炎病人52例,分为2组。治疗组27例中男性18例,女性9例,年龄(28±s11)a,与餐同服或餐后即服伊曲康唑200mg,qd,连续7d,同时外用2%酮康唑洗剂,qd,连续用药4wk。对照组25例中男性19例,女性6例,年龄(29±10)a,单纯口服伊曲康唑200mg,qd,疗程同上。观察用药后1,4wk,2组疗效。结果:对照组1,4wk有效率分别为52%和68%,治疗组分别为59%和96%,2组1wk疗效差异无显著意义,4wk疗效治疗组优于对照组。结论:口服伊曲康唑与外用酮康唑洗剂治疗糠秕孢子菌性毛囊炎疗效好。