Osman Mohammed A, El Maghraby Gamal M, Hedaya Mohsen A
Department of Pharmaceutical Technology, College of Pharmacy, University of Tanta, Tanta, Egypt.
Biopharm Drug Dispos. 2006 Mar;27(2):93-102. doi: 10.1002/bdd.487.
Sildenafil citrate is the first oral treatment for erectile dysfunction. Its oral bioavailability is about 40%. This research investigated the intestinal transport parameters of sildenafil citrate in rabbit using an in situ intestinal perfusion technique. This was studied in four different anatomical sites, namely duodenum, jejunoileum, ascending colon and rectum. The results revealed the highest absorptive clearance in the jejunoileum. The values of the permeability area product normalized to segment length (ml/min.cm) were 0.0101, 0.0063, 0.0059 and 0.0023 and those of the percentage absorbed were 68.0, 32.3, 23.0 and 5.0 in jejunoileum, duodenum, ascending colon and rectum, respectively. The values of the length (cm) required for complete absorption were 87.6, 137, 153 and 384 for each anatomical site in the same order. The absorptive clearance did not correlate with the net water flux in the four anatomical regions studied, indicating a mainly passive diffusion mechanism through a transcellular pathway. The plasma sildenafil concentrations achieved during intestinal perfusion experiments and sildenafil total body clearance in the rabbit were used to calculate the fraction of sildenafil that reached the systemic circulation relative to the amount that disappeared from the intestinal segment. Only 34% of sildenafil that disappeared from the intestinal segment appeared in the systemic circulation indicating that the presystemic elimination of sildenafil is 66%. These results confirm that the incomplete bioavailability of sildenafil is mainly due presystemic elimination.
枸橼酸西地那非是治疗勃起功能障碍的首个口服药物。其口服生物利用度约为40%。本研究采用原位肠灌注技术研究了枸橼酸西地那非在兔体内的肠道转运参数。在四个不同的解剖部位进行了研究，即十二指肠、空回肠、升结肠和直肠。结果显示空回肠的吸收清除率最高。以肠段长度归一化后的通透面积乘积值（ml/min.cm）在空回肠、十二指肠、升结肠和直肠分别为0.0101、0.0063、0.0059和0.0023，吸收百分比分别为68.0%、32.3%、23.0%和5.0%。各解剖部位完全吸收所需的长度（cm）依次为87.6、137、153和384。在所研究的四个解剖区域中，吸收清除率与净水通量无关，表明主要通过跨细胞途径的被动扩散机制。利用肠道灌注实验期间兔体内的血浆西地那非浓度和西地那非全身清除率来计算相对于从肠段消失的量而言进入体循环的西地那非的分数。从肠段消失的西地那非仅有34%出现在体循环中，这表明西地那非的首过消除率为66%。这些结果证实西地那非生物利用度不完全主要是由于首过消除。
