Peking University First Hospital, Institute of Clinical Pharmacology, Beijing, China.
Pfizer Inc, Shanghai, China.
Clin Pharmacol Drug Dev. 2020 Jul;9(5):573-581. doi: 10.1002/cpdd.806. Epub 2020 May 28.
Sildenafil citrate is approved to treat erectile dysfunction. An orally disintegrating tablet (ODT) of sildenafil citrate that does not require swallowing or administration with fluids has been developed. The bioequivalence and bioavailability of sildenafil citrate ODT (50 mg) without and with water were compared with conventional sildenafil citrate tablets (50 mg) in an open-label, randomized crossover study. Healthy Chinese male subjects (n = 36) were allocated to 1 of 6 sildenafil citrate treatment sequences under fasted conditions, and plasma samples for determination of sildenafil concentrations were collected predose through 14 hours postdose. Bioequivalence was demonstrated for sildenafil citrate ODT administered without water relative to the sildenafil citrate tablet administered with water; 90%CIs for the ratios of adjusted geometric means for sildenafil AUC , C , and AUC (ratio, 101.41%; 90%CI, 95.49%-107.70%; ratio, 93.55%; 90%CI, 84.15%-104.00%; and ratio, 101.03%; 90%CI, 94.80%-107.66%; respectively) were wholly contained within the bioequivalence acceptance range of 80% to 125%, indicating bioequivalence criteria were met. Relative bioavailability of sildenafil citrate ODT administered with water to the sildenafil citrate tablet (50 mg) administered with water was 97.10%, 91.43%, and 97.09% with respect to sildenafil AUC , C , and AUC , respectively (90%CI, 91.43%-03.12%, 82.25%-101.65%, and 90.90%-103.71%, respectively). Both sildenafil citrate formulations were generally well tolerated in healthy Chinese men. Sildenafil citrate ODT administered without or with water was bioequivalent to or met bioequivalence criteria compared with conventional sildenafil citrate tablets administered with water under fasted conditions in healthy Chinese men, thus offering a convenient alternative method of oral administration.
枸橼酸西地那非已获批准用于治疗勃起功能障碍。现已研发出一种无需吞服且无需用水送服的枸橼酸西地那非口崩片（ODT）。本研究采用开放、随机交叉试验，比较了枸橼酸西地那非 ODT（50mg）在不与水同服和与水同服时的生物等效性和生物利用度，与枸橼酸西地那非普通片剂（50mg）进行比较，健康中国男性受试者（n=36）按 1:1 随机分配至 6 种枸橼酸西地那非治疗序列，在禁食条件下采集服药前至服药后 14 小时的血样，用于测定西地那非浓度。结果表明，枸橼酸西地那非 ODT 不与水同服时与枸橼酸西地那非片剂与水同服时相比具有生物等效性；西地那非 AUC 、 C 、 AUC 的调整几何均数比值的 90%CI（比值，101.41%；90%CI，95.49%-107.70%；比值，93.55%；90%CI，84.15%-104.00%；比值，101.03%；90%CI，94.80%-107.66%）完全包含在 80%至 125%的生物等效性接受范围内，表明符合生物等效性标准。枸橼酸西地那非 ODT 与水同服时与枸橼酸西地那非片剂与水同服时相比，西地那非 AUC 、 C 、 AUC 的相对生物利用度分别为 97.10%、91.43%和 97.09%（90%CI，91.43%-03.12%、82.25%-101.65%和 90.90%-103.71%）。两种枸橼酸西地那非制剂在中国健康男性中通常具有良好的耐受性。枸橼酸西地那非 ODT 无论是否与水同服，在健康中国男性中均与枸橼酸西地那非片剂与水同服时具有生物等效性或符合生物等效性标准，为经口给药提供了一种方便的替代方法。
