Unacceptable side-effects associated with a hyperosmolar vaginal microbicide in a phase 1 trial.
We carried out a phase 1 trial of a candidate vaginal microbicide gel against HIV-1 and other sexually transmitted diseases, which contained cellulose acetate 1,2-benzenedicarboxylate (also known as cellulose acetate phthalate) in a glycerol-based vehicle. We had to terminate the study after five women had completed dosing, due to all women experiencing unacceptable vulvo-vaginal side-effects. Further investigations showed that the gel had a very high osmolality, which we believe led to excessive fluid transudation across the vaginal mucosa and acute mucosal dysfunction. We also showed that the rheology of the gel changed dramatically on fluid dilution. The osmolality and rheology of candidate microbicides and other genital mucosal products should therefore be analysed and considered at an early stage of product development.
Centre for Immunology and Infection, Hull York Medical School, University of York, York, UK. charles.lacey@hyms.ac.uk
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D000282:Administration, Intravaginal; D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000737:chemistry; D002482:Cellulose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009994:Osmolar Concentration; D012749:Sexually Transmitted Diseases / Q000517:prevention & control*; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage* / Q000737:chemistry; D055815:Young Adult
D000890:Anti-Infective Agents; D014622:Vaginal Creams, Foams, and Jellies; D002482:Cellulose; C011708:cellulose acetate phthalate