Feasibility of radiolabeled small molecule permeability as a quantitative measure of microbicide candidate toxicity

作者：Coleman Jenell S^*; Fuchs Edward; Aung Wutyi S; Marzinke Mark A; Bakshi Rahul P; Spiegel Hans M L; Robinson Jennifer; Hendrix Craig W

来源：Contraception, 2016, 93(4): 331-336.

DOI：10.1016/j.contraception.2016.01.002

• HIV
• N-9
• Permeability
• HIV
• Microbicide
• Spermicide

Objective: To determine the feasibility of using quantitative changes in vaginal permeability to small molecules as a measure of candidate microbicide toxicity.
Study design: Controlled, open-labeled, prospective study. Seven healthy women received a single vaginal dose of hydroxyethylcellulose gel (HEC), nonoxynol-9 (N-9) or K-Y Jelly. Each gel was radiolabeled with a small molecule (Tc-99m-DTPA) followed by 12-h blood and urine collection. Pharmacokinetic (PK) parameters of Tc-99m-DTPA were calculated to compare the impact of each gel on vaginal permeability. Each woman served as her own control. The Friedman test with post hoc Wilcoxon test was used to detect differences among the gels.
Results: Vaginal permeability of Tc-99m-DTPA was highest for the N-9 radiolabel. N-9 plasma area under the concentration curve was 2.7-fold higher (p=.04), and peak concentration was threefold higher (p=.04) compared to HEC. There were no significant PK parameter differences between HEC and K-Y Jelly or between N-9 and K-Y Jelly. Cumulative dose-adjusted median (interquartile range) 12-h timed urine gamma activity was 66.70 x 10(-4) mu Ci (27.90-152.00) following HEC dosing, 103.00 x 10(-4) mu Ci (98.20-684.00) following N-9 gel dosing and 20.30 x 10(-4) mu Ci (11.10-55.90) following K-Y gel dosing. The differences between urine HEC and K-Y Jelly (p =.047) and between N-9 and K-Y Jelly (p=.016) were statistically significant.
Conclusions: It is feasible to measure differences in vaginal permeability among vaginal gels using a radiolabeled small molecule, though there are permeability differences that require a nuanced understanding of gel composition to interpret the results.

• 出版日期2016-4