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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.

Publication ,  Journal Article
Pereira, LE; Singletary, T; Martin, A; Dinh, CT; Deyounks, F; Holder, A; McNicholl, J; Buckheit, KW; Buckheit, RW; Ham, A; Katz, DF; Smith, JM
Published in: Drug delivery and translational research
October 2018

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.

Duke Scholars

Published In

Drug delivery and translational research

DOI

EISSN

2190-3948

ISSN

2190-393X

Publication Date

October 2018

Volume

8

Issue

5

Start / End Page

1180 / 1190

Related Subject Headings

  • Vaginal Creams, Foams, and Jellies
  • Tenofovir
  • Pyrimidinones
  • Macaca
  • Female
  • Anti-HIV Agents
  • Animals
  • Administration, Rectal
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences
 

Citation

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Pereira, L. E., Singletary, T., Martin, A., Dinh, C. T., Deyounks, F., Holder, A., … Smith, J. M. (2018). 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. Drug Delivery and Translational Research, 8(5), 1180–1190. https://doi.org/10.1007/s13346-018-0538-0
Pereira, Lara E., Tyana Singletary, Amy Martin, Chuong T. Dinh, Frank Deyounks, Angela Holder, Janet McNicholl, et al. “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.Drug Delivery and Translational Research 8, no. 5 (October 2018): 1180–90. https://doi.org/10.1007/s13346-018-0538-0.
Pereira LE, Singletary T, Martin A, Dinh CT, Deyounks F, Holder A, et al. 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. Drug delivery and translational research. 2018 Oct;8(5):1180–90.
Pereira, Lara E., et al. “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.Drug Delivery and Translational Research, vol. 8, no. 5, Oct. 2018, pp. 1180–90. Epmc, doi:10.1007/s13346-018-0538-0.
Pereira LE, Singletary T, Martin A, Dinh CT, Deyounks F, Holder A, McNicholl J, Buckheit KW, Buckheit RW, Ham A, Katz DF, Smith JM. 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. Drug delivery and translational research. 2018 Oct;8(5):1180–1190.
Journal cover image

Published In

Drug delivery and translational research

DOI

EISSN

2190-3948

ISSN

2190-393X

Publication Date

October 2018

Volume

8

Issue

5

Start / End Page

1180 / 1190

Related Subject Headings

  • Vaginal Creams, Foams, and Jellies
  • Tenofovir
  • Pyrimidinones
  • Macaca
  • Female
  • Anti-HIV Agents
  • Animals
  • Administration, Rectal
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences