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Clin Pharmacol Ther. 2008 Jan;83(1):97-105. Epub 2007 May 16.

Quantitative imaging and sigmoidoscopy to assess distribution of rectal microbicide surrogates.

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Department of Medicine, Division of Clinical Pharmacology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.


Understanding the distribution of microbicide and human immunodeficiency virus (HIV) within the gastrointestinal tract is critical to development of rectal HIV microbicides. A hydroxyethylcellulose-based microbicide surrogate or viscosity-matched semen surrogate, labeled with gadolinium-DTPA (diethylene triamine pentaacetic acid) and 99mTechnetium-sulfur colloid, was administered to three subjects under varying experimental conditions to evaluate effects of enema, coital simulation, and microbicide or semen simulant over 5 h duration. Quantitative assessment used single photon emission computed tomography (SPECT)/computed tomography (CT) and magnetic resonance imaging (MRI) imaging, and sigmoidoscopic sampling. Over 4 h, radiolabel migrated cephalad in all studies by a median (interquartile range) of 50% (29-102%; P<0.001), as far as the splenic flexure (approximately 60 cm) in 12% of studies. There was a correlation in concentration profile between endoscopic sampling and SPECT assessments. HIV-sized particles migrate retrograde, 60 cm in some studies, 4 h after simulated ejaculation in our model. SPECT/CT, MRI, and endoscopy can be used quantitatively to facilitate rational development of microbicides for rectal use.

[Indexed for MEDLINE]

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