Isoosmolar Enemas Demonstrate Preferential Gastrointestinal Distribution, Safety, and Acceptability Compared with Hyperosmolar and Hypoosmolar Enemas as a Potential Delivery Vehicle for Rectal Microbicides

Francisco J. Leyva, Rahul P. Bakshi, Edward J. Fuchs, Liye Li, Brian S. Caffo, Arthur J. Goldsmith, Ana Ventuneac, Alex Carballo-Diéguez, Yong Du, Jeffrey P. Leal, Linda A. Lee, Michael S. Torbenson, Craig W. Hendrix

Research output: Contribution to journalArticle

Abstract

Rectally applied antiretroviral microbicides for preexposure prophylaxis (PrEP) of HIV infection are currently in development. Since enemas (rectal douches) are commonly used by men who have sex with men prior to receptive anal intercourse, a microbicide enema could enhance PrEP adherence by fitting seamlessly within the usual sexual practices. We assessed the distribution, safety, and acceptability of three enema types - hyperosmolar (Fleet), hypoosmolar (distilled water), and isoosmolar (Normosol-R) - in a crossover design. Nine men received each enema type in random order. Enemas were radiolabeled [99mTc-diethylene triamine pentaacetic acid (DTPA)] to assess enema distribution in the colon using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Plasma 99mTc-DTPA indicated mucosal permeability. Sigmoidoscopic colon tissue biopsies were taken to assess injury as well as tissue penetration of the 99mTc-DTPA. Acceptability was assessed after each product use and at the end of the study. SPECT/CT imaging showed that the isoosmolar enema had greater proximal colonic distribution (up to the splenic flexure) and greater luminal and colon tissue concentrations of 99mTc-DTPA when compared to the other enemas (p<0.01). Colon biopsies also showed that only the hyperosmolar enema caused sloughing of the colonic epithelium (p<0.05). In permeability testing, the hypoosmolar enema had higher plasma 99mTc-DTPA 24-h area under the concentration-time curve and peak concentration compared to the hyperosmolar and isoosmolar enemas, respectively. Acceptability was generally good with no clear preferences among the three enema types. The isoosmolar enema was superior or similar to the other enemas in all categories and is a good candidate for further development as a rectal microbicide vehicle.

Original languageEnglish (US)
Pages (from-to)1487-1495
Number of pages9
JournalAIDS research and human retroviruses
Volume29
Issue number11
DOIs
StatePublished - Nov 4 2013

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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