Comparative safety evaluation of the candidate vaginal microbicide C31G

Bradley J. Catalone, Tina M. Kish-Catalone, Elizabeth B. Neely, Lynn R. Budgeon, Mary L. Ferguson, Catherine Stiller, Shendra R. Miller, Daniel Malamud, Fred C. Krebs, Mary K. Howett, Brian Wigdahl

Research output: Contribution to journalArticle

Abstract

C31G is currently the focus of clinical trials designed to evaluate this agent as a microbicidal and spermicidal agent. In the following studies, the in vivo safety of C31G was assessed with a Swiss Webster mouse model of cervicovaginal toxicity and correlated with results from in vitro cytotoxicity experiments and published clinical observations. A single exposure of unformulated 1% C31G resulted in mild-to-moderate epithelial disruption and inflammation at 2 and 4 h postapplication. The columnar epithelium of the cervix was the primary site of damage, while no perturbation of the vaginal mucosa was observed. In contrast, application of unformulated 1.7% C31G resulted in greater levels of inflammation in the cervical epithelium at 2 h postapplication and severe epithelial disruption that persisted to 8 h postapplication. Application of a nonionic aqueous gel formulation containing 1% C31G resulted in no apparent cervicovaginal toxicity at any time point evaluated. However, formulation of 1.7% C31G did not substantially reduce the toxicity associated with unformulated C31G at that concentration. These observations correlate with findings gathered during a recent clinical trial, in which once-daily applications resulted in no adverse events in women receiving the formulation containing 1% C31G, compared to moderate-to-severe adverse events in 30% of women receiving the 1.7% C31G formulation. The Swiss Webster mouse model was able to effectively discriminate between concentrations and formulations of C31G that produced distinct clinical effects in human trials. The Swiss Webster animal model may be a highly valuable tool for preclinical evaluation of candidate vaginal microbicides.

Original languageEnglish (US)
Pages (from-to)1509-1520
Number of pages12
JournalAntimicrobial Agents and Chemotherapy
Volume49
Issue number4
DOIs
StatePublished - Apr 2005

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Anti-Infective Agents
Safety
Spermatocidal Agents
Epithelium
C 31G
Clinical Trials
Inflammation
Cervix Uteri
Mucous Membrane
Animal Models
Gels

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Catalone, B. J., Kish-Catalone, T. M., Neely, E. B., Budgeon, L. R., Ferguson, M. L., Stiller, C., ... Wigdahl, B. (2005). Comparative safety evaluation of the candidate vaginal microbicide C31G. Antimicrobial Agents and Chemotherapy, 49(4), 1509-1520. https://doi.org/10.1128/AAC.49.4.1509-1520.2005

Comparative safety evaluation of the candidate vaginal microbicide C31G. / Catalone, Bradley J.; Kish-Catalone, Tina M.; Neely, Elizabeth B.; Budgeon, Lynn R.; Ferguson, Mary L.; Stiller, Catherine; Miller, Shendra R.; Malamud, Daniel; Krebs, Fred C.; Howett, Mary K.; Wigdahl, Brian.

In: Antimicrobial Agents and Chemotherapy, Vol. 49, No. 4, 04.2005, p. 1509-1520.

Research output: Contribution to journalArticle

Catalone, BJ, Kish-Catalone, TM, Neely, EB, Budgeon, LR, Ferguson, ML, Stiller, C, Miller, SR, Malamud, D, Krebs, FC, Howett, MK & Wigdahl, B 2005, 'Comparative safety evaluation of the candidate vaginal microbicide C31G', Antimicrobial Agents and Chemotherapy, vol. 49, no. 4, pp. 1509-1520. https://doi.org/10.1128/AAC.49.4.1509-1520.2005
Catalone BJ, Kish-Catalone TM, Neely EB, Budgeon LR, Ferguson ML, Stiller C et al. Comparative safety evaluation of the candidate vaginal microbicide C31G. Antimicrobial Agents and Chemotherapy. 2005 Apr;49(4):1509-1520. https://doi.org/10.1128/AAC.49.4.1509-1520.2005
Catalone, Bradley J. ; Kish-Catalone, Tina M. ; Neely, Elizabeth B. ; Budgeon, Lynn R. ; Ferguson, Mary L. ; Stiller, Catherine ; Miller, Shendra R. ; Malamud, Daniel ; Krebs, Fred C. ; Howett, Mary K. ; Wigdahl, Brian. / Comparative safety evaluation of the candidate vaginal microbicide C31G. In: Antimicrobial Agents and Chemotherapy. 2005 ; Vol. 49, No. 4. pp. 1509-1520.
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