背景:临床试验显示,在与男性(MSM)发生性关系而非女性发生性关系的男性中,单次口服多西环素可预防性传播感染。阴道药代动力学数据,性传播感染的直肠和阴茎部位缺乏。我们检查了阴道,男性和女性的直肠和尿道多西环素浓度可以更好地预防性传播感染。
方法:在亚特兰大的一项非随机单剂量开放标签单中心研究中,在接受200mg口服多西环素剂量后1、2、4、8、24、48、72、96和168小时,对18-59岁男性和女性参与者的血液和尿液以及直肠和阴道拭子进行了评估。格鲁吉亚。直肠,阴道,给药后24小时收集宫颈活检和男性尿道拭子(试验注册:NCT04860505)。多西环素通过液相色谱-质谱法测量。
结果:11名男性和9名女性参与者参与了这项研究。给药后96小时内收集的直肠和阴道拭子上的强力霉素浓度约为血浆浓度的两倍,并且至少在4小时内保持在最低抑制浓度(MIC)以上,三,沙眼衣原体治疗两天,梅毒螺旋体,对四环素敏感的淋病奈瑟菌,分别。男性尿道分泌物中多西环素的几何平均浓度(1.166μg/mL;95%CI0.568-2.394μg/mL),男性直肠(0.596μg/g;0.442-0.803μg/g),给药后24小时收集的活检中的阴道(0.261μg/g;0.098-0.696μg/g)和宫颈组织(0.410μg/g;0.193-0.870μg/g)超过MIC。血浆和尿液多西环素水平定义了服药后4天和7天的依从性标志物,分别。在这项研究中没有报告不良事件。
结论:多西环素有效地分布到直肠,阴道和尿道.研究结果可以帮助解释多西环素预防STI的功效。
背景:由CDC校内基金资助,CDC合同HCVJCG-2020-45044(至CFK)。
BACKGROUND: Clinical trials showed a single oral dose of doxycycline taken after sex protects against STIs among men who have sex with men (MSM) but not women. Pharmacokinetic data at vaginal, rectal and penile sites of STI exposure are lacking. We examined vaginal, rectal and urethral doxycycline concentrations in men and women to better inform STI prevention.
METHODS: Doxycycline pharmacokinetics in male and female participants 18-59 years of age were evaluated in blood and urine and on rectal and vaginal swabs collected at 1, 2, 4, 8, 24, 48, 72, 96 and 168 h after receiving a 200 mg oral doxycycline dose in a non-randomised single dose open label single centre study in Atlanta, Georgia. Rectal, vaginal, and cervical biopsies and male urethral swabs were collected 24 h after dosing (Trial registration: NCT04860505). Doxycycline was measured by liquid chromatography-mass spectrometry.
RESULTS: Eleven male and nine female participants participated in the study. Doxycycline concentrations on rectal and vaginal swabs collected up to 96 h after dosing were approximately twice those of plasma and remained above minimum inhibitory concentrations (MICs) for at least four, three, and two days for Chlamydia trachomatis, Treponema pallidum, and tetracycline-sensitive Neisseria gonorrhoeae, respectively. Geometric mean doxycycline concentrations in male urethral secretions (1.166 μg/mL; 95% CI 0.568-2.394 μg/mL), male rectal (0.596 μg/g; 0.442-0.803 μg/g), vaginal (0.261 μg/g; 0.098-0.696 μg/g) and cervical tissue (0.410 μg/g; 0.193-0.870 μg/g) in biopsies collected 24 h after dosing exceeded MICs. Plasma and urine doxycycline levels defined adherence markers up to four and seven days postdosing, respectively. No adverse events were reported in this study.
CONCLUSIONS: Doxycycline efficiently distributes to the rectum, vagina and urethra. Findings can help explain efficacy of STI prevention by doxycycline.
BACKGROUND: Funded by CDC intramural funds, CDC contract HCVJCG-2020-45044 (to CFK).