Vehicle of triamcinolone acetonide is associated with retinal toxicity and transient increase of lens density

Background Intravitreal triamcinolone acetonide (TA) has been widely used as a therapeutic method for many ocular diseases, but a consensus on an appropriate safe therapeutic window of dosage for intravitreal injection, and whether vehicle of TA should be reduced or eliminated, has not yet been reached. The aim of this article is to investigate these issues.Methods Forty New Zealand white rabbits were divided into four experimental groups and one control group. Four or 25 mg TA, with vehicle either reduced or not, was injected into the vitreous cavity of rabbits in experimental groups. Rabbits in the control group received 0.2 ml intravitreal sterile saline solution. Intraocular pressures (IOP) were measured by a Tonopen tonometer. Values of lens density were measured by a Pentacam system. Soluble protein, total antioxidation capacity, reduced glutathione (GSH), glutathion peroxidase (GSH-px), and superoxide dismutase (SOD) in lens were measured by specific kits. ERG and pathological examinations, including light and electron microscopy of the retina, were also performed.Results Elevation of IOP was noted in all experimental groups after intravitreal TA (P<0.01, paired t-test). Significant increase of lens density was noticed at 1 week after intravitreal TA in the 25 mg vehicle-containing group (P<0.0001, paired t-test). Significant loss of GSH-px activity was noticed at the end of the study (P<0.05, paired t-test), while SOD activity increased (P<0.05, paired t-test). Amplitudes of ERG waves declined significantly in vehicle-containing groups (P<0.01, paired t-test) at the end of the study. Pathological examination showed obvious retinal toxicity in vehicle-containing groups.Conclusions Vehicle of TA should be eliminated or reduced before intravitreal injection to avoid potential retinal toxicity and transient increase in lens density.Presented at Chinese Academy of Fundus Disease Meeting, April, 2005.This study was supported by the 985 Fund of Peking University, Beijing.The authors have no financial interest in any instruments or drugs mentioned in this study.     

曲安奈德PLGA微球对兔上腭部创面瘢痕形成影响的实验研究

目的:探讨曲安奈德PLGA微球对创面瘢痕愈合中瘢痕生成的抑制作用,研究局部应用曲安奈德的最佳给药途径。方法:3组共24只兔的上腭部创面模型,分别应用曲安奈德PLGA微球以及曲安奈德悬浊液,在瘢痕形成不同时间后切取瘢痕标本进行HE、VG染色及酶组织化学染色并电镜观察其组织形态学改变来分析曲安奈德不同给药途径的差异。结果:三组兔上腭创面愈合时间不同,表面颜色、质地不一样。电镜、常规染色以及免疫组织化学染色皆说明曲安奈德PLGA微球有明显的瘢痕抑制作用,且效果高于曲安奈德悬浊液。结论:曲安奈德PLGA微球能抑制瘢痕的增殖过程,使瘢痕组织纤维化过程明显减轻。合并手术一次性给药治疗瘢痕有很好的临床价值。     

口腔径路曲安奈德蝶腭神经节封闭治疗变应性鼻炎（附415例报告）

目的：探讨口腔径路曲安奈德蝶腭神经节封闭治疗变应性鼻炎的效果。方法：变应性鼻炎患者415例，男270例，女145例。用自制封闭针头于口腔径路行曲安奈德蝶腭神经节封闭术。结果：415例中，有效250例，好转63例，总有效率为99．5％。结论：经口腔径路用曲安奈德行蝶腭神经节封闭术是治疗变应性鼻炎的有效疗法。     

醋酸曲安缩松注射液的一阶导数分光光度测定

采用一阶导数分光光度法测定醋酸曲安缩松注射液的含量，平均回收率为９９．８２％，ＲＳＤ为０．３９％。方法简便快速，结果满意。     

Further studies on the chronotherapy of asthma with inhaled steroids: The effect of dosage timing on drug efficacy

Background: Chronotherapy studies with inhaled corticosteroids have shown optimal therapeutic benefit when steroids are administered four times per day (QID) or once daily at 3 PM.Objective: This study evaluated whether more convenient once-daily dosage times (8 AM and 5:30 PM) produce improvement in asthma equivalent to QID.Methods: Efficacy outcome measures included FEV₁, peak expiratory flow rates, bronchial responsiveness, use of β₂-agonists, nocturnal awakenings, and responses to a quality of life questionnaire. Systemic effects were blood eosinophil count, cortisol level, 24-hour urinary cortisol, and evaluation for oral candidiasis and dysphonia.Results: Baseline measurements for all three treatment groups were similar. For morning peak expiratory flow rate, significant improvement was seen for the QID group (p = 0.001) and the 5:30 PM group (p = 0.003), but not the 8 AM group (p = 0.75). For evening peak expiratory flow rate, significant improvement was seen for the QID group (p = 0.005) and the 5:30 PM group (p = 0.01), but not for the 8 AM group (p = 0.47). There were significant improvements in all other outcome variables for each group except PC₂₀. There was a significant improvement in PC₂₀ only in the QID group. The systemic effects of the three regimens were comparable.Conclusion: Dosing of inhaled steroid at 5:30 PM had no increased systemic effects and produced efficacy similar to QID dosing. Dosing at 8 AM did not produce results consistently comparable to QID dosing. Optimal once-daily dosing of inhaled steroid is between 3 PM and 5:30 PM.     

Effect of intranasal fluticasone propionate and triamcinolone acetonide on basal and dynamic measures of hypothalamic–pituitary–adrenal-axis activity in healthy volunteers

BACKGROUND : Most published studies show that intranasal corticosteroids have no effect on the hypothalamic-pituitary-adrenal (HPA) axis, but there have been isolated reports to the contrary, contradicting accumulated knowledge on pharmacokinetics. OBJECTIVE : To re-evaluate the effect of fluticasone propionate aqueous nasal spray (FPANS) and triamcinolone acetonide (TAA) aqueous nasal spray on the HPA axis using an improved study design. METHODS : Twenty-three healthy volunteers were randomized in a double-blind, three-way crossover study. The study comprised a 4-day placebo run-in phase followed by three 4-day treatment periods (placebo, FPANS (200 microg once daily) or TAA aqueous nasal spray (220 microg once daily)), separated by 7-14 days washout intervals. Before the first, and on the last day of each treatment period, 12-h overnight urine was collected to assess cortisol excretion and cortisol creatinine ratio. Approximately 26 h after the last administration of study medication, volunteers underwent stimulation with 0.5 microg adrenocorticotropic hormone (ACTH). Serum cortisol concentrations were measured before and 20 and 30 min after injection. Blood and urine samples were analysed for cortisol by liquid chromatography tandem mass spectrometry. RESULTS : Compared with placebo, EP or TAA had no significant effect on mean overnight (12 h) urinary cortisol excretion, and did not significantly suppress the overnight geometric mean urinary cortisol/creatinine excretion ratio. Values for serum cortisol before and after ACTH simulation showed no significant suppression, although there was a slight blunting of the HPA-axis response following TAA treatment. CONCLUSION : This study confirms that there are no detectable effects on the HPA axis following short-term intranasal FP or TAA at their recommended dosages.     

HPLC法测定尿素-醋酸曲安萘德软膏中醋酸曲安萘德的含量

目的 采用高效液相色谱法测定尿素醋酸曲安萘德软膏中醋酸曲安萘德的含量。方法 Kromasil C₁₈(150mm×4.6mm,5μm)色谱柱;流动相为甲醇水乙醚(62∶38∶2);流量1.0ml·min^-1;检测波长为240nm。采用炔诺酮作内标物质。结果 醋酸曲安萘德在0.16～0.79μg范围内呈线性关系,r=0.9998(n=5),平均回收率为100.7%(n=5),RSD为0.97%。结论 本法简便、准确,可以控制该制剂的质量。     

曲安奈德治疗增生性瘢痕的疗效观察

目的:观察曲安奈德对增生性瘢痕的治疗效果.方法:对63例增生性瘢痕患者采用曲安奈德瘢痕内注射进行治疗.结果:治愈:39例;有效:18例;无效:6例.结论:曲安奈德是治疗增生性瘢痕的有效药物.     

Safety & efficacy of single subconjunctival triamcinolone 5 mg depot vs topical loteprednol post cataract surgery: less drop cataract surgery

AIM: To do a randomized prospective interventional study for comparing the effects of a single subconjunctival triamcinolone acetonide (SCTA) injection to tapering topical loteprednol in patients undergoing phacoemulsification surgery under topical anesthesia. METHODS: A total of 400 patients were randomized into 2 groups; Group A (200 patients) received 5 mg SCTA at the end of surgery and topical ketorolac tromethamine (0.5%) with ofloxacin (0.3%) combination for 3wk. Group B (200 patients) received tapering topical loteprednol etabonate (0.5%) along with ofloxacin (0.3%) and ketorolac tromethamine (0.5%) for 3wk. Outcomes evaluated were intraocular pressure (IOP), anterior chamber cells/flare and macular oedema postoperatively at 1, 6 and 12wk. RESULTS: Baseline parameters were almost similar in both the groups. No statistical difference was seen between the preoperative and postoperative IOP values for Group A (P=0.82) and Group B (P=0.61) and postoperative IOP values in between both groups (P=0.14) at 1wk. Incidence of cells/flare postoperative was statistically not significant (P=0.82) in both groups at all follow up visits. Postoperative macular oedema was not observed at any follow up visit. CONCLUSION: SCTA appears to be an effective alternative to prolong postoperative topical steroid use.