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This study investigated the pharmacokinetics, metabolism and excretion of ramelteon, a novel selective ML1 receptor agonist. Six healthy male subjects received a single oral dose of 16 mg (14C)‐ramelteon. Ramelteon was rapidly absorbed (tmax of 0.3 hours) and eliminated (half‐life of 1.2 hours). The metabolites MI, MI, MI11 and MIV were rapidly formed and eliminated (half‐lives of 1 to 3 hours). Systemic exposure of metabolite M‐II (major active metabolite) was 20‐ to 30‐fold greater than that of ramelteon, while the exposures of M‐I, M‐III, and M‐IV were one‐ to four‐fold higher than that of ramelteon. Of total radioactivity administered, 84% was renally eliminated, and 4% was faecally eliminated, with metabolites of ramelteon accounting for the majority of the dose eliminated. High urinary recovery of radioactivity indicates that there was at least 84% oral absorption of ramelteon. Negligible urinary excretion of ramelteon and low serum concentrations of ramelteon (relative to metabolites) indicate that ramelteon undergoes extensive first‐pass metabolism. Ramelteon was metabolized primarily via oxidation to hydroxyl and carbonyl groups, with secondary metabolism to form glucuronide conjugates. Clinical Pharmacology & Therapeutics (2004) 75, P22–P22; doi:

ObjectivesOnline testing for STIs may help overcome barriers of traditional face-to-face testing, such as stigma and inconvenience. However, regulation of these online tests is lacking, and the quality of services is variable, with potential short-term and long-term personal, clinical and public health implications. This study aimed to evaluate online self-testing and self-sampling service providers in the UK against national standards.MethodsProviders of online STI tests (self-sampling and self-testing) in the UK were identified by an internet search of Google and Amazon (June 2020). Website information on tests and associated services was collected and further information was requested from providers via an online survey, sent twice (July 2020, April 2021). The information obtained was compared with British Association for Sexual Health and HIV and Faculty of Sexual and Reproductive Healthcare guidelines and standards for diagnostics and STI management.Results31 providers were identified: 13 self-test, 18 self-sample and 2 laboratories that serviced multiple providers. Seven responded to the online survey. Many conflicts with national guidelines were identified, including: lack of health promotion information, lack of sexual history taking, use of tests licensed for professional-use only marketed for self-testing, inappropriate infections tested for, incorrect specimen type used and lack of advice for postdiagnosis management.ConclusionsVery few online providers met the national STI management standards assessed, and there is concern that this will also be the case for service provision aspects that were not covered by this study. For-profit providers were the least compliant, with concerning implications for patient care and public health. Regulatory change is urgently needed to ensure that all online providers are compliant with national guidelines to ensure high-quality patient care, and providers are held to account if non-compliant.

Background Sexually Transmitted Infections, including Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT), continue to be a global health problem. Increased access to point-of-care-tests (POCTs) could help detect infection and lead to appropriate management of cases and contacts, reducing transmission and development of reproductive health sequelae. Yet diagnostics with good clinical effectiveness evidence can fail to be implemented into routine care. Here we assess values beyond clinical effectiveness for molecular CT/NG POCTs implemented across diverse routine practice settings. Methods We conducted a systematic review of peer-reviewed primary research and conference abstract publications in Medline and Embase reporting on molecular CT/NG POCT implementation in routine clinical practice until 16th February 2021. Results were extracted into EndNote software and initially screened by title and abstract by one author according to the inclusion and exclusion criteria. Articles that met the criteria, or were unclear, were included for full-text assessment by all authors. Results were synthesised to assess the tests against guidance criteria and develop a CT/NG POCT value proposition for multiple stakeholders and settings. Findings The systematic review search returned 440 articles; 28 were included overall. The Cepheid CT/NG GeneXpert was the only molecular CT/NG POCT implemented and evaluated in routine practice. It did not fulfil all test guidance criteria, however, studies of test implementation showed multiple values for test use across various healthcare settings and locations. Our value proposition highlights that the majority of values are setting-specific. Sexual health services and outreach services have the least overlap, with General Practice and other non-sexual health specialist services serving as a “bridge” between the two. Conclusions Those wishing to improve CT/NG diagnosis should be supported to identify the values most relevant to their settings and context, and prioritise implementation of tests that are most closely aligned with those values.