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Mucosal Pharmacology of Doxycycline for Prevention of Bacterial Sexually Transmitted Infections Among Men and Women
34 Pages Posted: 26 Jul 2023
More...Abstract
Background: Recent clinical trials showed a single oral dose of doxycycline taken after sex provided protection against STIs among men who have sex with men (MSM) but not women. Mucosal pharmacokinetic data at sites of STI exposure are lacking. We examined mucosal doxycycline concentrations in men and women to better interpret doxycycline prevention efficacy and inform dose optimization.
Methods: Eleven male and nine female participants provided blood, urine, and mucosal swabs up to seven days after receiving a 200 mg oral doxycycline dose. Rectal, vaginal, and cervical biopsies and urethral swabs were collected 24 hours after dosing. Doxycycline was measured by liquid chromatography-mass spectrometry.
Findings: Rectal and vaginal doxycycline exposure up to 96 hours were approximately twice that of plasma and remained above minimum inhibitory concentrations (MICs) for at least four, three, and two days for Chlamydia trachomatis, Treponema pallidum, and Neisseria gonorrhoeae, respectively. Doxycycline concentrations in urethral secretions (1·166 µg/mL; 0·568 – 2·394 µg/mL), rectal (0·616 µg/g; 0·495 – 0·766 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) all exceeded MICs. Plasma and urine doxycycline levels represented adherence markers for up to four and seven days postdosing, respectively.
Interpretation: Doxycycline efficiently distributes to mucosal sites and maintains inhibitory concentrations against bacterial STIs up to four days after dosing. Mucosal data support STI protection among MSM and suggest lack of efficacy among women is not likely due to inadequate doxycycline concentrations in vaginal tissues. Findings inform rational doxycycline dose modalities and optimization for STI prevention.\
Trial Registration: Registered at clinicaltrials.gov (NCT04860505).
Funding: Funded by CDC intramural funds, CDC contract HCVJCG-2020-45044 (to CFK).
Declaration of Interest: The authors have no competing interests to declare. The findings and conclusions in this manuscript are those of the authors and do not necessarily represent the official position of the United States Centers for Disease Control and Prevention or the Department of Health and Human Services.
Ethical Approval: Approved by Emory University and CDC Institutional Review Boards. All participants were recruited from existing Emory University study databases and the Atlanta community and gave written informed consent, and the trial conforms to the US Federal Policy for the Protection of Human Subjects.
Keywords: doxycycline, sexually transmitted infection (STI), event-driven pre-exposure prophylaxis (PrEP), antibiotics, post-exposure prophylaxis (PEP), pharmacology
Suggested Citation: Suggested Citation