Safety and Availability of Dapivirine (TMC120) Delivered from an Intravaginal Ring
| Autor: | Hans Verstraelen, Mark Mitchnick, B. Variano, J. van Roey, Paul Coplan, K. Douville, Marleen Temmerman, Steven Weyers, L. van Bortel, Joseph Romano, Zeda F. Rosenberg |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
medicine.medical_specialty Anti-HIV Agents Immunology Dapivirine Cervix Uteri Introitus Placebos Plasma Young Adult Pregnancy Tandem Mass Spectrometry Virology medicine Humans Cervix Gynecology Antiinfective agent Vaginal delivery Vaginal microbicide business.industry Middle Aged Microbicides for sexually transmitted diseases Administration Intravaginal Pyrimidines Infectious Diseases medicine.anatomical_structure Vagina Female business Chromatography Liquid |
| Zdroj: | AIDS Research and Human Retroviruses. 25:483-488 |
| ISSN: | 1931-8405 0889-2229 |
| DOI: | 10.1089/aid.2008.0184 |
| Popis: | 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 were50 pg/ml. Dapivirine from both IVRs was successfully distributed throughout the lower genital tract at concentrations1000x 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|