Pfizer Inc, New York, New York.
Pfizer Inc, Groton, Connecticut.
Clin Ther. 2014 Feb 1;36(2):236-44. doi: 10.1016/j.clinthera.2013.12.010. Epub 2014 Jan 18.
Sildenafil citrate is indicated for the treatment of erectile dysfunction. An orally disintegrating tablet (ODT) of sildenafil citrate has been developed for the benefit of patients who have difficulty swallowing solid dosage forms.
The main goal of this study was to evaluate the bioequivalence of sildenafil ODT with and without water versus marketed sildenafil oral film-coated tablets. A secondary objective was to evaluate the effects of a high-fat meal on the pharmacokinetics of sildenafil ODT.
The bioequivalence study of sildenafil ODT given with and without water versus marketed sildenafil citrate film-coated oral tablets was conducted in 36 subjects. In a food-effect study, the effect of a standard high-fat meal on the pharmacokinetics of sildenafil ODT was evaluated in 12 subjects. Both studies were randomized, open-label, crossover, single-dose (50 mg) studies in healthy men aged ≥45 years. Plasma samples were collected for 14 hours postdose, and pharmacokinetics were determined by using noncompartmental analyses.
All subjects in both studies were Asian males between the ages of 45 and 69 years. Sildenafil ODT without water was bioequivalent to the marketed sildenafil film-coated oral tablet as the 90% CI for the ratio of geometric means of Cmax, AUC0-∞, and AUC0-last were contained within equivalence limits (80%-125%). When sildenafil ODTs were given with water, the 90% CIs for sildenafil AUC0-∞ and AUC0-last were contained within the range of 80% to 125%; however, the 90% CI for sildenafil Cmax was not (79.76-92.78). This difference in Cmax is unlikely to have any clinically meaningful impact. High-fat meals reduced the rate but not the extent of absorption of sildenafil. Mean Cmax was reduced by 59%, and median Tmax was delayed from 0.625 hour (fasting) to 4 hours (high-fat meal). However, AUC values were comparable between fed and fasted treatments.
Sildenafil ODT, given with or without water, provides equivalent systemic exposure compared with marketed sildenafil film-coated oral tablets, thus offering a convenient alternative method of administration. Considering the results of the food-effect study, sildenafil ODT should be taken on an empty stomach. ClinicalTrials.gov identifiers: NCT01254383 (bioequivalence) and NCT01254396 (food effect).
枸橼酸西地那非片用于治疗勃起功能障碍。为了使吞咽固体剂型有困难的患者受益，已开发出枸橼酸西地那非口腔崩解片。
本研究的主要目的是评估枸橼酸西地那非口腔崩解片与市售的枸橼酸西地那非口服薄膜片在无和有水条件下的生物等效性。次要目标是评估高脂肪餐对枸橼酸西地那非口腔崩解片药代动力学的影响。
在 36 名受试者中进行了枸橼酸西地那非口腔崩解片在无和有水条件下与市售枸橼酸西地那非薄膜片口服的生物等效性研究。在一项食物效应研究中，12 名受试者评估了标准高脂肪餐对枸橼酸西地那非口腔崩解片药代动力学的影响。这两项研究均为健康男性（年龄≥45 岁）单次（50mg）、随机、开放标签、交叉、设计的研究。给药后 14 小时内采集血浆样本，采用非房室分析方法测定药代动力学参数。
两项研究的所有受试者均为年龄在 45 岁至 69 岁之间的亚洲男性。枸橼酸西地那非口腔崩解片无水溶液与市售枸橼酸西地那非薄膜片口服片具有生物等效性，因为 Cmax、AUC0-∞和 AUC0-last 的几何均数比值的 90%置信区间（CI）均在等效限度内（80%-125%）。当枸橼酸西地那非口腔崩解片用水送服时，AUC0-∞和 AUC0-last 的 90%CI 在 80%至 125%范围内；然而，Cmax 的 90%CI 不在此范围内（79.76-92.78）。这种 Cmax 差异不太可能具有任何临床意义。高脂肪餐降低了西地那非的吸收速度，但不影响其吸收程度。Cmax 平均降低 59%，Tmax 中位数从空腹（0.625 小时）延迟至高脂餐（4 小时）。然而，与禁食相比，AUC 值在进食和禁食之间是可比的。
枸橼酸西地那非口腔崩解片，无论是否用水送服，均可与市售枸橼酸西地那非薄膜片口服片提供等效的全身暴露，从而提供了一种方便的替代给药方法。考虑到食物效应研究的结果，枸橼酸西地那非口腔崩解片应空腹服用。临床试验注册号：NCT01254383（生物等效性）和 NCT01254396（食物效应）。
