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 Torbenson, Craig W. Hendrix

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 [ 99m Tc-diethylene triamine pentaacetic acid (DTPA)] to assess enema distribution in the colon using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Plasma 99m Tc-DTPA indicated mucosal permeability. Sigmoidoscopic colon tissue biopsies were taken to assess injury as well as tissue penetration of the 99m Tc-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 99m Tc-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 99m Tc-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
Externally publishedYes

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Enema
Anti-Infective Agents
Safety
Colon
Acids
Permeability
Biopsy
Transverse Colon
Cross-Over Studies
HIV Infections

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

Cite this

Isoosmolar Enemas Demonstrate Preferential Gastrointestinal Distribution, Safety, and Acceptability Compared with Hyperosmolar and Hypoosmolar Enemas as a Potential Delivery Vehicle for Rectal Microbicides. / Leyva, Francisco J.; Bakshi, Rahul P.; Fuchs, Edward J.; Li, Liye; Caffo, Brian S.; Goldsmith, Arthur J.; Ventuneac, Ana; Carballo-Diéguez, Alex; Du, Yong; Leal, Jeffrey P.; Lee, Linda A.; Torbenson, Michael; Hendrix, Craig W.

In: AIDS Research and Human Retroviruses, Vol. 29, No. 11, 04.11.2013, p. 1487-1495.

Research output: Contribution to journalArticle

Leyva, Francisco J. ; Bakshi, Rahul P. ; Fuchs, Edward J. ; Li, Liye ; Caffo, Brian S. ; Goldsmith, Arthur J. ; Ventuneac, Ana ; Carballo-Diéguez, Alex ; Du, Yong ; Leal, Jeffrey P. ; Lee, Linda A. ; Torbenson, Michael ; Hendrix, Craig W. / Isoosmolar Enemas Demonstrate Preferential Gastrointestinal Distribution, Safety, and Acceptability Compared with Hyperosmolar and Hypoosmolar Enemas as a Potential Delivery Vehicle for Rectal Microbicides. In: AIDS Research and Human Retroviruses. 2013 ; Vol. 29, No. 11. pp. 1487-1495.
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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 [ 99m Tc-diethylene triamine pentaacetic acid (DTPA)] to assess enema distribution in the colon using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Plasma 99m Tc-DTPA indicated mucosal permeability. Sigmoidoscopic colon tissue biopsies were taken to assess injury as well as tissue penetration of the 99m Tc-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 99m Tc-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 99m Tc-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.",
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