Preclinical evaluation of UC781 microbicide vaginal drug delivery

Drug Delivery and Translational Research

Volumn 1, Issue 2, 2011, Pages 175-182

  Clark, Meredith R ^a   McCormick, Timothy J ^a   Doncel, Gustavo F ^a   Friend, David R ^a  

^a EASTERN VIRGINIA MEDICAL SCHOOL   (United States)

Author keywords

Drug release; Microbicide; Permeability; Pharmacokinetics; Safety; UC781; Vaginal gel

Indexed keywords

N [4 CHLORO 3 (3 METHYL 2 BUTENYLOXY)PHENYL] 2 METHYL 3 FURANCARBOTHIOAMIDE; NONOXINOL 9; PLACEBO;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG DELIVERY SYSTEM; DRUG FORMULATION; DRUG PENETRATION; DRUG RELEASE; DRUG SAFETY; DRUG TISSUE LEVEL; DRUG TOLERABILITY; FEMALE; GEL; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; PRIORITY JOURNAL; RABBIT; SINGLE DRUG DOSE; TISSUE CULTURE; TREATMENT DURATION; VAGINA;

EID: 84455187598     PISSN: 2190393X     EISSN: 21903948     Source Type: Journal    
DOI: 10.1007/s13346-011-0019-1     Document Type: Article

References (15)

1. Balzarini J, Brouwer WG, Dao DC, Osika EM, de Clercq E. Identification of novel thiocarboxanilide derivatives that suppress a variety of drug-resistant mutant human immunodeficiency virus type 1 strains at a potency similar to that for wild-type virus. Antimicrob Agents Chemother. 1996; 40: 1454-66.
2. Balzarini J, Naesens L, Verbeken E, LAGA M, van Damme L, Parniak M, et al. Preclinical studies on thiocarboxanilide UC-781 as a virucidal agent. AIDS. 1998; 12: 1129-38.
3. Borkow G, Arion D, Wainberg MA, Parniak MA. The thiocarboxanilide nonnucleoside inhibitor UC781 restores antiviral activity of 3′-azido-3′-deoxythymidine (AZT) against AZT-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother. 1999; 43: 259-63.
4. Pelemans H, Esnouf R, DE Clercq E, Balzarini J. Mutational analysis of trp-229 of human immunodeficiency virus type 1 reverse transcriptase (RT) identifies this amino acid residue as a prime target for the rational design of new non-nucleoside RT inhibitors. Mol Pharmacol. 2000; 57: 954-60.
5. van Herrewege Y, Michiels J, van Roey J, Fransen K, Kestens L, Balzarini J, et al. In vitro evaluation of nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 as human immunodeficiency virus microbicides. Antimicrob Agents Chemother. 2004; 48: 337-9.
6. Fletcher P, Kiselyeva Y, Wallace G, Romano J, Griffin G, Margolis L, et al. The nonnucleoside reverse transcriptase inhibitor UC-781 inhibits human immunodeficiency virus type 1 infection of human cervical tissue and dissemination by migratory cells. J Virol. 2005; 79: 11179-86.
7. Zussman A, Lara L, Lara HH, Bentwich Z, Borkow G. Blocking of cell-free and cell-associated HIV-1 transmission through human cervix organ culture with UC781. AIDS. 2003; 17: 653-61.
8. Borkow G, Barnard J, Nguyen TM, Belmonte A, Wainberg MA, Parniak MA. Chemical barriers to human immunodeficiency virus type 1 (HIV-1) infection: retrovirucidal activity of UC781, a thiocarboxanilide nonnucleoside inhibitor of HIV-1 reverse transcriptase. J Virol. 1997; 71: 3023-30.
9. Schwartz JL, Kovalevsky G, Lai JJ, Ballagh SA, Mccormick T, Douville K, et al. A randomized six-day safety study of an antiretroviral microbicide candidate UC781, a non-nucleoside reverse transcriptase inhibitor. Sex Transm Dis. 2008; 35: 414-9.
10. Thakker KD, Chern WC. Development and validation of in vitro release tests for semisolid dosage forms-Case study. Dissolution Technologies, May, 2003; 10-16.
11. Tien D, Schnaare RL, Kang F, Cohl G, Mccormick TJ, Moench TR, 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: 845-53.
12. Ayehunie S, Cannon C, Lamore S, Kubilus J, Anderson DJ, Pudney J, et al. Organotypic human vaginal-ectocervical tissue model for irritation studies of spermicides, microbicides, and feminine-care products. Toxicol In Vitro. 2006; 20: 689-98.
13. Ayehunie S, Cannon C, Larosa K, Pudney J, Anderson DJ, Klausner M. Development of an in vitro alternative assay method for vaginal irritation. Toxicology. 2011; 279: 130-8.
14. Fletcher PS, Harman SJ, Boothe AR, Doncel GF, Shattock RJ. Preclinical evaluation of lime juice as a topical microbicide candidate. Retrovirology. 2008; 5: 3.
15. Nuttall JP, Thake DC, LEWIS MG, Ferkany JW, Romano JW, 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: 909-14.