Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.
EBioMedicine. 2024 Mar;101:105037. doi: 10.1016/j.ebiom.2024.105037. Epub 2024 Feb 29.
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.
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.
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.
Doxycycline efficiently distributes to the rectum, vagina and urethra. Findings can help explain efficacy of STI prevention by doxycycline.
Funded by CDC intramural funds, CDC contract HCVJCG-2020-45044 (to CFK).
临床试验表明，对于男男性行为者（MSM），性行为后单次口服多西环素可预防性传播感染（STI），但对女性无效。目前尚缺乏关于 STI 暴露部位（阴道、直肠和阴茎）的药代动力学数据。我们检测了男性和女性在阴道、直肠和尿道中的多西环素浓度，以更好地了解 STI 预防。
在佐治亚州亚特兰大的一项非随机单次剂量开放标签单中心研究中，对 18-59 岁的男性和女性参与者在接受 200mg 口服多西环素后 1、2、4、8、24、48、72、96 和 168 小时时，评估了血液和尿液中的多西环素药代动力学，并采集了直肠和阴道拭子。在给药后 24 小时（试验注册：NCT04860505）采集直肠、阴道和宫颈活检以及男性尿道拭子。通过液相色谱-质谱法测量多西环素。
11 名男性和 9 名女性参与者参与了这项研究。直肠和阴道拭子中在给药后长达 96 小时采集的多西环素浓度大约是血浆中的两倍，至少持续 4、3 和 2 天的时间，其浓度均超过了沙眼衣原体、梅毒螺旋体和四环素敏感淋病奈瑟菌的最低抑菌浓度（MIC）。男性尿道分泌物中的多西环素几何平均浓度（1.166μg/ml；95%CI 0.568-2.394μg/ml）、直肠（0.596μg/g；0.442-0.803μg/g）、阴道（0.261μg/g；0.098-0.696μg/g）和宫颈组织（0.410μg/g；0.193-0.870μg/g）在给药后 24 小时采集的活检样本中均超过了 MIC。血浆和尿液中的多西环素水平在给药后 4 天和 7 天分别定义了依从性标志物。本研究未报告任何不良事件。
多西环素能有效地分布到直肠、阴道和尿道。研究结果可以帮助解释多西环素预防 STI 的疗效。
由美国疾病控制与预防中心内部资金资助，美国疾病控制与预防中心合同 HCVJCG-2020-45044（至 CFK）。
