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Intestinal absorption and presystemic disposition of sildenafil citrate in the rabbit: evidence for site-dependent absorptive clearance

2005; Wiley; Volume: 27; Issue: 2 Linguagem: Inglês

10.1002/bdd.487

1099-081X

Mohammed A. Osman, Gamal M. El Maghraby, Mohsen A. Hedaya,

Urinary Bladder and Prostate Research

Biopharmaceutics & Drug DispositionVolume 27, Issue 2 p. 93-102 Original PaperFree Access Intestinal absorption and presystemic disposition of sildenafil citrate in the rabbit: evidence for site-dependent absorptive clearance Mohammed A. Osman, Mohammed A. Osman Department of Pharmaceutical Technology, College of Pharmacy, University of Tanta, Tanta, EgyptSearch for more papers by this authorGamal M. El Maghraby, Gamal M. El Maghraby Department of Pharmaceutical Technology, College of Pharmacy, University of Tanta, Tanta, EgyptSearch for more papers by this authorMohsen A. Hedaya, Corresponding Author Mohsen A. Hedaya mhedaya@e-pharmacokinetics.com Department of Clinical Pharmacy, College of Pharmacy, University of Tanta, Tanta, EgyptDepartment of Clinical Pharmacy, College of Pharmacy, University of Tanta, Tanta, EgyptSearch for more papers by this author Mohammed A. Osman, Mohammed A. Osman Department of Pharmaceutical Technology, College of Pharmacy, University of Tanta, Tanta, EgyptSearch for more papers by this authorGamal M. El Maghraby, Gamal M. El Maghraby Department of Pharmaceutical Technology, College of Pharmacy, University of Tanta, Tanta, EgyptSearch for more papers by this authorMohsen A. Hedaya, Corresponding Author Mohsen A. Hedaya mhedaya@e-pharmacokinetics.com Department of Clinical Pharmacy, College of Pharmacy, University of Tanta, Tanta, EgyptDepartment of Clinical Pharmacy, College of Pharmacy, University of Tanta, Tanta, EgyptSearch for more papers by this author First published: 21 December 2005 https://doi.org/10.1002/bdd.487Citations: 15AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract 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. Copyright © 2005 John Wiley & Sons, Ltd. Citing Literature Volume27, Issue2March 2006Pages 93-102 RelatedInformation