A Compartmental Pharmacokinetic Evaluation of Long-Acting Rilpivirine in HIV-Negative Volunteers for Pre-Exposure Prophylaxis

• DOI: 10.1038/clpt.2014.118
• Publication Date: 2014-05-26T13:08:48Z
• Authors: A G A Jackson; L J Else; P M M Mesquita; D Egan; D J Back; Z Karolia; L Ringner-Nackter; C J Higgs; B C Herold; B G Gazzard; M Boffito
• Keywords: Rilpivirine; Clinical Pharmacology

Rilpivirine long-acting (RPV-LA) is a parenteral formulation enabling prolonged plasma exposure. We explored its multiple-compartment pharmacokinetics (PK) after single dose, for pre-exposure prophylaxis. Sixty-six HIV-negative volunteers were enrolled: women received an intramuscular dose of 300, 600, or 1,200 mg, with and genital levels measured to 84 days postdose; men receiving 600 mg had similar PK determined in rectum. Ex vivo antiviral activity cervicovaginal lavage (CVL) was also assessed. After RPV concentrations peaked at 6–8 present genital-tract fluid day 84. Vaginal male rectal tissue matched those plasma. At the CVL showed greater activity, above baseline, 28 56. All doses well tolerated. gave rilpivirine viral inhibition repeated will be important further selection. Clinical Pharmacology & Therapeutics (2014); 96 3, 314–323. advance online publication 25 June 2014. doi:10.1038/clpt.2014.118