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02619 CICLOPIROXOLAMINE: A MARKETED VAGINAL PRODUCT WITH POTENTIAL AS A MICROBICIDE Zaneveld, Lourens* To move the development of microbicides forward rapidly in India, where AIDS and other STDs are a serious problem, 2,200 marketed topical products from that country were reviewed and 50 pharmaceutical ingredients or formulations were tested for anti-HIV and cytotoxic activity. Those selected were evaluated for their gonococcal, chlamydial, lactobacillus, and sperm inhibitory properties, and the best products for their safety in the rabbit vaginal irritation (RVI) assay. Ciclopiroxolamine (CO) was one agent with desirable properties. It inhibits HIV-1 (IC50 = ~1 mg/ml), gonococci (IC50 = 1 mg/ml), chlamydia (IC50 = 1.6 mg/ml), has broad spectrum antibacterial and antifungal activity, and is minimally spermicidal. A RVI study with a marketed vaginal CO (1%) formulation confirmed the vaginal safety reported previously in the rat, rabbit, dog, and human. According to the literature, CO penetrates the vaginal wall but is minimally absorbed into the systemic circulation; has an excellent safety profile; and is not mutagenic, genotoxic, teratogenic, or carcinogenic. CO is widely marketed as a vaginal and cutaneous antifungal agent, and GMP-manufactured product can be purchased at reasonable cost. Its antibacterial and anti-inflammatory properties may help prevent bacterial vaginosis and maintain vaginal health. Development of CO for vaginal prophylactic purposes will be initiated in collaboration with the Indian drug industry. Dr. Lourens Zaneveld |
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