Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Microbiology, Örebro University, Orebro, Sweden.
BMJ Open. 2022 Nov 11;12(11):e064782. doi: 10.1136/bmjopen-2022-064782.
infections are common and incidence increasing. Oropharyngeal infections are associated with greater treatment failure compared with other sites and drive transmission to anogenital sites through saliva. Gonococcal resistance is increasing and new treatments are scarce, therefore, clinicians must optimise currently available and emerging treatments in order to have efficacious therapeutic options. This requires pharmacokinetic data from the oral cavity/oropharynx, however, availability of such information is currently limited.
Healthy male volunteers (participants) recruited into the study will receive single doses of either ceftriaxone 1 g, cefixime 400 mg or ceftriaxone 500 mg plus 2 g azithromycin. Participants will provide samples at 6-8 time points (treatment regimen dependent) from four oral sites, two oral fluids, one anorectal swab and blood. Participants will complete online questionnaires about their medical history, sexual practices and any side effects experienced up to days 5-7. Saliva/oral mucosal pH and oral microbiome analysis will be undertaken. Bioanalysis will be conducted by liquid chromatography-mass spectrometry. Drug concentrations over time will be used to develop mathematical models for optimisation of drug dosing regimens and to estimate pharmacodynamic targets of efficacy.
This study was approved by Royal Melbourne Hospital Human Research Ethics Committee (60370/MH-2021). The study results will be submitted for publication in peer-reviewed journals and reported at conferences. Summary results will be sent to participants requesting them. All data relevant to the study will be included in the article or uploaded as supplementary information.
ACTRN12621000339853.
感染很常见，且发病率呈上升趋势。与其他部位相比，口咽部感染与更高的治疗失败率相关，并通过唾液传播到肛门生殖器部位。淋球菌的耐药性正在增加，新的治疗方法也很稀缺，因此，临床医生必须优化现有的和新出现的治疗方法，以便获得有效的治疗选择。这需要口腔/口咽部的药代动力学数据，但目前这种信息的可用性有限。
招募到研究中的健康男性志愿者（参与者）将接受单次剂量的头孢曲松 1 克、头孢克肟 400 毫克或头孢曲松 500 毫克加 2 克阿奇霉素。参与者将根据治疗方案在 6-8 个时间点（4 个口腔部位、2 种口腔液、1 种肛门直肠拭子和血液）提供样本。参与者将在第 5-7 天完成关于他们的病史、性行为和任何经历的副作用的在线问卷。将进行唾液/口腔黏膜 pH 值和口腔微生物组分析。将通过液相色谱-质谱法进行生物分析。将根据时间推断药物浓度来开发优化药物剂量方案的数学模型，并估计疗效的药效学目标。
这项研究得到了皇家墨尔本医院人类研究伦理委员会的批准（60370/MH-2021）。研究结果将提交给同行评审期刊发表，并在会议上报告。总结结果将发送给请求的参与者。与研究相关的所有数据都将包含在文章中或作为补充信息上传。
ACTRN12621000339853。
