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. 2018 Oct;8(5):1180-1190.
doi: 10.1007/s13346-018-0538-0.

Effects of gel volume on pharmacokinetics for vaginal and rectal applications of combination DuoGel-IQB4012, a dual chamber-dual drug HIV microbicide gel, in pigtailed macaques

Lara E Pereira  1 , Tyana Singletary  2 , Amy Martin  3 , Chuong T Dinh  4 , Frank Deyounks  4 , Angela Holder  3 , Janet McNicholl  3 , Karen W Buckheit  5 , Robert W Buckheit Jr  5 , Anthony Ham  5 , David F Katz  6 , James M Smith  7
Affiliations

Effects of gel volume on pharmacokinetics for vaginal and rectal applications of combination DuoGel-IQB4012, a dual chamber-dual drug HIV microbicide gel, in pigtailed macaques

Lara E Pereira et al. Drug Deliv Transl Res. 2018 Oct.

Abstract

This study evaluated effects of differing gel volumes on pharmacokinetics (PK). IQB4012, a gel containing the non-nucleoside reverse transcriptase inhibitor IQP-0528 and tenofovir (TFV), was applied to the pigtailed macaque vagina and rectum. Vaginal gel volumes (1% loading of both drugs) were 0.5 or 1.5 ml; following wash-out, 1 or 4 ml of gel were then applied rectally. Blood, vaginal, and rectal fluids were collected at 0, 2, 4, and 24 h. Vaginal and rectal tissue biopsies were collected at 4 and 24 h. There were no statistically significant differences in concentrations for either drug between gel volumes within compartments at matched time points. After vaginal gel application, median IQP-0528 concentrations were ~ 104-105 ng/g, 105-106 ng/ml, and 103-105 ng/ml in vaginal tissues, vaginal fluids, and rectal fluids, respectively (over 24 h). Median vaginal TFV concentrations were 1-2 logs lower than IQP-0528 levels at matched time points. After rectal gel application, median IQP-0528 and TFV concentrations in rectal fluids were ~ 103-105 ng/ml and ~ 102-103 ng/ml, respectively. Concentrations of both drugs sampled in rectal tissues were low (~ 101-103 ng/g). For 1 ml gel, half of sampled rectal tissues had undetectable concentrations of either drug, and over half of sampled rectal fluids had undetectable TFV concentrations. These results indicate differences in drug delivery between the vaginal and rectal compartments, and that smaller vaginal gel volumes may not significantly compromise microbicide PK and prophylactic potential. However, effects of rectal gel volume on PK for both drugs were less definitive.

Keywords: HIV prevention; IQP0528; Macaque; Pharmacokinetics; PrEP; Rectal gel; Vaginal gel.

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Conflict of interest statement

Conflict of interest Lara E. Pereira, Tyana Singletary, Amy Martin, Chuong T. Dinh, Angela Holder, and Janet McNicholl declare no conflicts of interest. Karen W. Buckheit, Robert W. Buckheit, Jr., and Anthony S. Ham are employed by ImQuest Biosciences and received funding from NIH grant # 5U19AI101961 and declare no conflicts of interest. David F. Katz and James M. Smith received funding from NIH grant # 5U19AI101961 and declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Analysis of IQP-0528 (open) and TFV (striped) levels in a vaginal tissues, b vaginal fluids, and c rectal fluids from N = 6 macaques treated vaginally with 0.5 (black) or 1.5 ml (gray) IQB-4012 gel. Results shown for vaginal samples include pooled data from proximal, medial, and distal sites. Concentrations at each of these sites are listed in Table 2. One-way ANOVA test with Dunns post-test analysis was performed. Significant paired data sets (p < 0.05) were further analyzed ad-hoc using Wilcoxon matched-pairs signed-rank t test, and yielded p values < 0.0001 where indicated (*)
Fig. 2
Fig. 2
Analysis of IQP-0528 (open), TFV (striped), and TFV-DP (dotted) levels in a rectal fluids and b rectal tissues from N = 6 macaques following rectal application of 1 (black) or 4 ml (gray) IQB-4012 gel. Concentrations at each of these sites are detailed in Table 3. One-way ANOVA test with Dunns post-test analysis was performed. Significant paired data sets (p < 0.05) were further analyzed ad-hoc using Wilcoxon matched-pairs signed-rank t test, and yielded EC50 < 0.0001 where indicated (*)
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References

    1. FDA approves first drug for reducing the risk of sexually acquired HIV infection [press release]. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm312210.htm2012.
    1. Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367(5):399–410. - PMC - PubMed
    1. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363(27):2587–99. - PMC - PubMed
    1. Marrazzo JM, Ramjee G, Richardson BA, Gomez K, Mgodi N, Nair G, et al. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2015;372(6): 509–18. - PMC - PubMed
    1. Molina JM, Capitant C, Spire B, Pialoux G, Cotte L, Charreau I, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med. 2015;373(23):2237–46. - PubMed

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