Open-Label Crossover Oral Bioequivalence Pharmacokinetics Comparison of a Single Dose of Super-bioavailable Itraconazole 130 mg and Innovator SUBA®-Itraconazole Capsules 130 mg (2 x 65 mg) in Healthy Adults Under Fed Conditions

D. Dhoot
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Abstract

Introduction: Itraconazole (ITZ), an antifungal agent taken orally, demonstrates intricate and variable absorption kinetics, significantly impacted by food intake. The invention of Super-Bioavailable Itraconazole (SITZ) has led to a surge in various brands offering different dosages of SB ITZ, overcoming barriers associated with conventional itraconazole. Hence, this study was planned to evaluate the bioequivalence of Itraconazole Capsules 130 mg (Test) of Glenmark Pharmaceuticals Ltd, India, with Innovator SITZ 130 mg (2× 65 mg; Reference) in healthy, adult, male, human subjects under fed condition in addition to safety and tolerability. Materials and methods: A total of 36 subjects were enrolled in an open-label, balanced, randomized, two-treatment, two-sequence, two-period, two-way crossover, single dose oral bioavailability study which was conducted in healthy, adult, human male subjects under fed conditions. Test and reference product were administered sequentially. 22 blood samples per subject were collected as pre and post dose within 2 hours of intake of food. The concentrations of ITZ and Hydroxy-itraconazole (OH-ITZ) in plasma were measured by High-Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS). Assessment of bioequivalence was done on the basis of the 90% CIs of the differences of least squares treatment means for Ln-transformed Cmax and AUC0-t of ITZ obtained after single-dose administration under fed conditions for Test (T) vs Reference (R) Results: The mean value of the area under curve (AUC0-t) of test drug (SITZ 130 mg) was 4604.98 ng.hr/mL whereas for reference drug (SITZ, 2 x 65 mg), it was 4812.04 ng.hr/mL which was statistically non-significant. The Pharmacokinetic parameters for OH-ITZ measured from both formulations followed a pattern in terms of bioavailability similar to that for the ITZ plasma blood levels for the test/reference ratios for Cmax (100.88%) and AUC0-t (97.44%). Subjects crossed over from one period of administration of either test or reference drugs to a second period with dosing with the opposite drug attained higher Cmax and AUC0-t values for ITZ, than the same subjects administered reference drug in this study. The administration of both the drugs were well tolerated by all the subjects with no added adverse events Conclusion: The pharmacokinetics activity was found to be comparable and bioequivalent between test product at 130 mg dose and innovator itraconazole 130 mg (2x 65 mg). Also, both the drugs were found to be safe and well tolerated with no adverse effects.
超生物可利用型伊曲康唑 130 毫克与创新药 SUBA®-Itraconazole 胶囊 130 毫克(2 x 65 毫克)在健康成人中的单剂量开放标签交叉口服生物等效性药代动力学比较
简介:伊曲康唑(ITZ)是一种口服抗真菌剂,其吸收动力学复杂多变,受食物摄入的影响很大。超生物利用型伊曲康唑(SITZ)的发明克服了传统伊曲康唑的相关障碍,导致各种品牌推出不同剂量的 SB ITZ。因此,本研究计划评估印度 Glenmark 制药有限公司生产的伊曲康唑胶囊 130 毫克(试验)与 Innovator SITZ 130 毫克(2×65 毫克;参照)在喂养条件下对健康成年男性受试者的生物等效性,以及安全性和耐受性:共有 36 名受试者参加了一项开放标签、平衡、随机、两疗程、两序列、两阶段、双向交叉、单剂量口服生物利用度研究。试验产品和参比产品依次给药。每个受试者在进食后 2 小时内采集 22 份血样,分别作为服药前和服药后的血样。采用高效液相色谱-串联质谱法(HPLC-MS/MS)测定血浆中 ITZ 和羟基伊曲康唑(OH-ITZ)的浓度。生物等效性的评估基于试验(T)与参照(R)结果在喂养条件下单次给药后获得的 ITZ Ln 变形 Cmax 和 AUC0-t 的最小二乘法处理均值的 90% CIs 差值:试验药物(SITZ 130 mg)的曲线下面积(AUC0-t)平均值为 4604.98 ng.hr/mL,而参比药物(SITZ,2 x 65 mg)的曲线下面积(AUC0-t)平均值为 4812.04 ng.hr/mL,差异无统计学意义。两种制剂测得的 OH-ITZ 药代动力学参数的生物利用度模式与 ITZ 血浆浓度的模式相似,即 Cmax(100.88%)和 AUC0-t(97.44%)的试验/参照比。与本研究中服用参比药物的相同受试者相比,从服用试验药物或参比药物的一个阶段过渡到服用相反药物的第二个阶段的受试者的 ITZ Cmax 值和 AUC0-t 值更高。结论:所有受试者对两种药物的耐受性都很好,没有出现额外的不良反应:研究发现,130 毫克剂量的试验产品与创新药伊曲康唑 130 毫克(2x 65 毫克)的药代动力学活性相当,具有生物等效性。此外,两种药物均安全且耐受性良好,无不良反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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