title: Safety and availability of dapivirine (TMC120) delivered from an intravaginal ring.
abstract: Vaginal delivery of 200 mg or 25 mg dapivirine from intravaginal rings (IVRs) was evaluated over a 7-day period in two phase 1 safety trials (IPM001 and IPM008, respectively) in a total of 25 healthy women 19 to 46 years of age. The IVR was generally safe and well tolerated with similar adverse events observed in the placebo and dapivirine groups. Across both studies, dapivirine concentrations in vaginal fluids measured at the introitus, cervix, and ring area were within the mean range of 0.7-7.1 microg/ml. Mean dapivirine concentrations in vaginal and cervical tissues on day 7 were 0.3-0.7 microg/g in IPM001 and 1.5-3.5 microg/g in IPM008. Mean plasma concentrations of dapivirine were <50 pg/ml. Dapivirine from both IVRs was successfully distributed throughout the lower genital tract at concentrations >1000x the EC(50) against wild-type HIV-1 (LAI) in MT4 cells suggesting that IVR delivery of microbicides is a viable option meriting further study.
authors.affiliation: International Partnership for Microbicides, Silver Spring, Maryland 20910, USA. jromano@ipm-microbicides.org
authors.forename: J
authors.initials: J
authors.lastname: Romano
authors.forename: B
authors.initials: B
authors.lastname: Variano
authors.forename: P
authors.initials: P
authors.lastname: Coplan
authors.forename: J
authors.initials: J
authors.lastname: Van Roey
authors.forename: K
authors.initials: K
authors.lastname: Douville
authors.forename: Z
authors.initials: Z
authors.lastname: Rosenberg
authors.forename: M
authors.initials: M
authors.lastname: Temmerman
authors.forename: H
authors.initials: H
authors.lastname: Verstraelen
authors.forename: L
authors.initials: L
authors.lastname: Van Bortel
authors.forename: S
authors.initials: S
authors.lastname: Weyers
authors.forename: M
authors.initials: M
authors.lastname: Mitchnick
mesh_terms: D000282:Administration, Intravaginal; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D002584:Cervix Uteri / Q000737:chemistry; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D010949:Plasma / Q000737:chemistry; D011247:Pregnancy; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry; D014621:Vagina / Q000737:chemistry; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D010919:Placebos; D011743:Pyrimidines; C481671:Dapivirine