Pharmacokinetics and topical vaginal effects of two tenofovir gels in rabbits

AIDS Research and Human Retroviruses

Volumn 28, Issue 11, 2012, Pages 1458-1466

  Clark, Meredith R ^a   Friend, David R ^a  

^a EASTERN VIRGINIA MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG METABOLITE; GLYCEROL; PYROPHOSPHATE; TENOFOVIR;

ANIMAL EXPERIMENT; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; CELL VACUOLE; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG FORMULATION; DRUG TISSUE LEVEL; EXPERIMENTAL RABBIT; FEMALE; GEL; HISTOLOGY; ILIAC LYMPH NODE; IN VIVO STUDY; LYMPH NODE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; OSMOLALITY; PRIORITY JOURNAL; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; TOPICAL TREATMENT; VAGINA EPITHELIUM; VAGINAL SECRETION;

ADENINE; ADMINISTRATION, INTRAVAGINAL; ADMINISTRATION, RECTAL; ANIMALS; ANTI-HIV AGENTS; BODY FLUIDS; FEMALE; HIV INFECTIONS; LYMPH NODES; ORGANOPHOSPHONATES; RABBITS; VAGINA; VAGINAL CREAMS, FOAMS, AND JELLIES;

EID: 84868519069     PISSN: 08892229     EISSN: 19318405     Source Type: Journal    
DOI: 10.1089/aid.2011.0328     Document Type: Article

References (27)

1. Cranage M, Sharpe S, Herrera C, et al.: Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel. PLoS Med Aug 5 2008;5(8):e157; discussion e157.
2. Parikh UM, Dobard C, Sharma S, et al.: Complete protection from repeated vaginal simian-human immunodeficiency virus exposures in macaques by a topical gel containing te-nofovir alone or with emtricitabine. J Virol 2009;83(20):10358-10365.
3. Tsai CC, Follis KE, Sabo A, et al.: Prevention of SIV infection in macaques by (R)-9-(2-phosphonylmethoxypropyl)ade-nine. Science 1995;270(5239):1197-1199.
4. Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al.: Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010;329(5996):1168-1174.
5. Andrei G, Lisco A, Vanpouille C, et al.: Topical tenofovir, a microbicide effective against HIV, inhibits herpes simplex virus-2 replication. Cell Host Microbe 2011;10(4):379-389.
6. Schwartz JL, Ballagh SA, Kwok C, et al.: Fourteen-day safety and acceptability study of the universal placebo gel. Contraception 2007;75(2):136-141.
7. Tien D, Schnaare RL, Kang F, et al.: In vitro and in vivo characterization of a potential universal placebo designed for use in vaginal microbicide clinical trials. AIDS Res Hum Retroviruses 2005;21(10):845-853.
8. Rohan LC, Moncla BJ, Kunjara N Ayudhya RP, et al.: In vitro and ex vivo testing of tenofovir shows it is effective as an HIV-1 microbicide. PLoS ONE 2010;5(2):e9310.
9. Mayer KH, Maslankowski LA, Gai F, et al.: Safety and tol-erability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS 2006; 20(4):543-551.
10. Rosen RK, Morrow KM, Carballo-Dieguez A, et al.: Acceptability of tenofovir gel as a vaginal microbicide among women in a phase I trial: A mixed-methods study. J Womens Health (Larchmt) 2008;17(3):383-392.
11. Anton P, Cranston R, Carballo-Dieguez A, et al.: RMP-02/MTN-006: A phase 1 placebo-controlled trial of rectally applied 1% vaginal TFV gel with comparison to oral TDF. 18th Conference on Retroviruses and Opportunistic Infections, 2011:34LB.
12. Fuchs EJ, Lee LA, Torbenson MS, et al.: Hyperosmolar sexual lubricant causes epithelial damage in the distal colon: Potential implication for HIV transmission. J Infect Dis 2007; 195(5):703-710.
13. Cone R, Hoen T, Wong X, Abusuwwa R, Anderson D, and Moench T: Vaginal microbicides: Detecting toxicities in vivo that paradoxically increase pathogen transmission. BMC Infect Dis 2006;6(1):90.
14. Moench TR, Mumper RJ, Hoen TE, Sun M, and Cone RA: Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse. BMC Infect Dis 2010;10:331.
15. Begay O, Jean-Pierre N, Abraham CJ, et al.: Identification of personal lubricants that can cause rectal epithelial cell damage and enhance HIV type 1 replication in vitro. AIDS Res Hum Retroviruses 2011;27(9):1019-1024.
16. Dezzutti CS, Rohan LC, Lynam JD, Wang L, and Friend D: Tenofovir gel reformulation results in improved product safety for rectal application. 18th Conference on Retro-viruses and Opportunistic Infections, 2011:983.
17. Mahalingam A, Smith E, Fabian J, et al.: Design of a semisolid vaginal microbicide gel by relating composition to properties and performance. Pharm Res 2010;27(11):2478-2491.
18. Clark MR, McCormick TJ, Doncel G, and Friend DR: Pre-clinical evaluation of UC781 microbicide vaginal drug delivery. Drug Del Transl Res 2011;1(2):175-182.
19. Nuttall JP, Thake DC, Lewis MG, Ferkany JW, Romano JW, and Mitchnick MA: Concentrations of dapivirine in the rhesus macaque and rabbit following once daily intravaginal administration of a gel formulation of [14C]dapivirine for 7 days. Antimicrob Agents Chemother 2008;52(3):909-914.
20. Antoniou T, Park-Wyllie LY, and Tseng AL: Tenofovir: A nucleotide analog for the management of human immunodeficiency virus infection. Pharmacotherapy 2003;23(1):29-43.
21. Karim SS, Kashuba AD, Werner L, and Karim QA: Drug concentrations after topical and oral antiretroviral pre-exposure prophylaxis: Implications for HIV prevention in women. Lancet 2011;378(9787):279-281.
22. Schwartz JL, Rountree W, Kashuba ADM, et al.: A multi-compartment, single and multiple dose pharmacokinetic study of the vaginal candidate microbicide 1% tenofovir gel. PLoS ONE 2011;6(10):e25974.
23. Hu Q, Frank I, Williams V, et al.: Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue. J Exp Med 2004;199(8):1065-1075.
24. Hladik F, Sakchalathorn P, Ballweber L, et al.: Initial events in establishing vaginal entry and infection by human immunodeficiency virus type-1. Immunity 2007;26(2):257-270.
25. Hladik F and Doncel GF: Preventing mucosal HIV transmission with topical microbicides: Challenges and opportunities. Antiviral Res 2010;88(Suppl 1):S3-9.
26. Kearney BP, Flaherty JF, and Shah J: Tenofovir disoproxil fumarate. Clin Pharmacokinet 2004;43(9):595-612.
27. Brown JA, Pack LR, Fowler JD, and Suo Z: Pre-steady-state kinetic analysis of the incorporation of anti-HIV nucleotide analogs catalyzed by human X-and Y-family DNA poly-merases. Antimicrob Agents Chemother 2011;55(1):276-283.