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New psychoactive substances (NPS), especially synthetic cannabinoids (SC) remain a public health concern. Due to ethical reasons, systematic controlled human studies to elucidate their toxicodynamics and/or toxicokinetics are usually not possible. However, such knowledge is necessary, for example, for determination of screening targets and interpretation of clinical and forensic toxicological data. In the present study, the feasibility of the pig model as an alternative for human in vivo metabolism studies of SC was investigated. For this purpose, the metabolic pattern of the SC methyl-2-{[1-(5-fluoropentyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]amino}-3,3-dimethylbutanoate (5F-MDMB-P7AICA) was elucidated in pig urine following inhalative administration (dosage: 200 µg/kg body weight). The results were compared to human and pig liver microsomal assays and literature. In addition, different incubations with isolated cytochrome-P450 monooxygenases (CYP) were conducted to identify the involved isozymes. In total, nine phase I and three phase II metabolites were identified in pig urine. The most abundant reactions were ester hydrolysis, ester hydrolysis combined with glucuronidation, and ester hydrolysis combined with hydroxylation at the tert-butyl moiety. The parent compound was only found up to one hour after administration in pig urine. The metabolite formed after hydroxylation and glucuronidation was detectable for 2 h, the one formed after ester hydrolyzation and defluorination for 4 h after administration. All other metabolites were detected during the whole sampling time. The most abundant metabolites were also detected using both microsomal incubations and monooxygenase screenings revealed that CYP3A4 catalyzed most reactions. Finally, pig data showed to be in line with published human data. To conclude, the main metabolites recommended in previous studies as urinary targets were confirmed by using pig urine. The used pig model seems therefore to be a suitable alternative for in vivo metabolism studies of 7-azaindole-derived SC.
New psychoactive substances (NPS), especially synthetic cannabinoids (SC) remain a public health concern. Due to ethical reasons, systematic controlled human studies to elucidate their toxicodynamics and/or toxicokinetics are usually not possible. However, such knowledge is necessary, for example, for determination of screening targets and interpretation of clinical and forensic toxicological data. In the present study, the feasibility of the pig model as an alternative for human in vivo metabolism studies of SC was investigated. For this purpose, the metabolic pattern of the SC methyl-2-{[1-(5-fluoropentyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]amino}-3,3-dimethylbutanoate (5F-MDMB-P7AICA) was elucidated in pig urine following inhalative administration (dosage: 200 µg/kg body weight). The results were compared to human and pig liver microsomal assays and literature. In addition, different incubations with isolated cytochrome-P450 monooxygenases (CYP) were conducted to identify the involved isozymes. In total, nine phase I and three phase II metabolites were identified in pig urine. The most abundant reactions were ester hydrolysis, ester hydrolysis combined with glucuronidation, and ester hydrolysis combined with hydroxylation at the tert-butyl moiety. The parent compound was only found up to one hour after administration in pig urine. The metabolite formed after hydroxylation and glucuronidation was detectable for 2 h, the one formed after ester hydrolyzation and defluorination for 4 h after administration. All other metabolites were detected during the whole sampling time. The most abundant metabolites were also detected using both microsomal incubations and monooxygenase screenings revealed that CYP3A4 catalyzed most reactions. Finally, pig data showed to be in line with published human data. To conclude, the main metabolites recommended in previous studies as urinary targets were confirmed by using pig urine. The used pig model seems therefore to be a suitable alternative for in vivo metabolism studies of 7-azaindole-derived SC.
AIM OF THE STUDY: The purpose of the present study was to evaluate demographic characteristics of inmates in the Canton of Zurich (exposure), and investigate the changes in diseases and drug use between 2015 and 2020 (outcome). METHODS: The study prospectively evaluated 51,989 inmates admitted to the Police Prison Zurich in Switzerland between 1 April 2015 and 31 August 2020 and who were systematically medically assessed. A total of 19,027 (37%) inmates had one or more health conditions, which the authors recorded according to the International Classification of Diseases-10 (ICD-10), in addition to demographic data (country of origin, sex, age, year of imprisonment), as well as details of any drugs used (type and dosage). RESULTS: The 19,027 inmates with medical conditions had a mean age of 35.4±12.5 years (range 10–89) and comprised 16,489 males (87%). The inmates originated from 170 countries, including 4606 from Switzerland (24.2%), 4227 from Eastern Europe (22%) and 3432 from the Middle East & North Africa (18%). A total of 1631 inmates (9%) were enrolled in the medication-assisted treatment (MAT) programme, and 672 patients (4%) received a psychiatric evaluation. The proportions of foreign prisoners did not increase during the study period. There was a significant increase in the use of antipsychotics from year 1 to 5 (y = 0.866x; R2 = 0.902; p = 0.01) and anticonvulsants from year 1 to 4 (y = 1.27x; R2 = 0.823; p = 0.01), and a significant decrease in the use of analgesics from year 2 to 5 (y = -4.42x; R2 = 0.947; p = 0.03) and antianxiety drugs from year 1 to 4 (y = -3.31x; R2 = 0.989; p = 0.005). Inmates from Switzerland were most likely to use antianxiety drugs, while inmates from the Middle East & North Africa were most likely to use antipsychotics (OR 2.09; CI 1.88–2.34) and anticonvulsants (OR 3.52; CI 2.90–4.29), whereas inmates from Latin and North America were most likely to use herbal medicine (OR 1.50; CI 1.05–2.10). CONCLUSIONS: The findings of this study could help anticipate needs of prisons as well as improve treatment of disease and assist with substance use or abuse, particularly in the context of migration.
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