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
Lara E PereiraJames Smith

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 conc...Continue Reading

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Citations

Sep 27, 2019·Expert Opinion on Drug Metabolism & Toxicology·Yali WangGuangdi Li
Nov 18, 2020·Current Opinion in Pharmacology·Murugesan VanangamudiVigneshwaran Namasivayam

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Methods Mentioned

BETA
biopsies
biopsy
sedation

Software Mentioned

GraphPad Prism

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