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Paracetamol (4'-hydroxyacetanilide, N-acetyl-p-aminophenol, acetaminophen, and paracetamol) is a widely used over-the-counter analgesic and antipyretic drug. Paracetamol and structural analogs are ubiquitous in the natural environment and easily accumulate in aquatic environment, which have been detected in surface waters, wastewater, and drinking water throughout the world. Paracetamol wastewater is mainly treated by chemical oxidation processes. Although these chemical methods may be available for treating these pollutants, the harsh reaction conditions, the generation of secondary pollutants, and the high operational cost associated with these methods have often made them not a desirable choice. Biodegradation of paracetamol is being considered as an environmentally friendly and low-cost option. The goal of this review is to provide an outline of the current knowledge of biodegradation of paracetamol in the occurrence, degrading bacteria, and proposed metabolic/biodegrading pathways, enzymes and possible intermediates. The comprehensive understanding of the metabolic pathways and enzyme systems involved in the utilization of paracetamol means will be helpful for optimizing and allowing rational design of biodegradation systems for paracetamol-contaminated wastewater.[PUBLICATION ABSTRACT]

The introduction of three-dimensional printing (3DP) has created exciting possibilities for the fabrication of dosage forms, paving the way for personalized medicine. In this study, oral dosage forms of two drug concentrations, namely 2.50% and 5.00%, were fabricated via stereolithography (SLA) using a novel photopolymerizable resin formulation based on a monomer mixture that, to date, has not been reported in the literature, with paracetamol and aspirin selected as model drugs. In order to produce the dosage forms, the ratio of poly(ethylene glycol) diacrylate (PEGDA) to poly(caprolactone) triol was varied with diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure TPO) utilized as the photoinitiator. The fabrication of 28 dosages in one print process was possible and the printed dosage forms were characterized for their drug release properties. It was established that both drugs displayed a sustained release over a 24-h period. The physical properties were also investigated, illustrating that SLA affords accurate printing of dosages with some statistically significant differences observed from the targeted dimensional range, indicating an area for future process improvement. The work presented in this paper demonstrates that SLA has the ability to produce small, individualized batches which may be tailored to meet patients’ specific needs or provide for the localized production of pharmaceutical dosage forms.

This article describes the swelling and release mechanisms of paracetamol in polyurethane nanocomposite hydrogels containing Cloisite® 30B (organically modified montmorillonite). The transport mechanism, swelling and release processes of the active substance in nanocomposite matrix were studied using gravimetric and UV-Vis spectroscopic methods. Swelling and release processes depend on the amount of clay nanoparticles in these systems and the degree of crosslinking of PU/PEG/Cloisite® 30B hydrogel nanocomposites. The presence of clay causes, on the one hand, a reduction in free volumes in the polymer matrices, making the swelling process less effective; on the other hand, the high swelling and self-aggregation behavior of Cloisite® 30B and the interactions of paracetamol both with it and with the matrix, cause a change in the transport mechanism from anomalous diffusion to Fickian-like diffusion. A more insightful interpretation of the swelling and release profiles of the active substance was proposed, taking into account the “double swelling” process, barrier effect, and aggregation of clay. It was also proven that in the case of modification of polymer matrices with nanoparticles, the appropriate selection of their concentration is crucial, due to the potential possibility of controlling the swelling and release processes in drug delivery patches.

PurposeParacetamol is the only drug recommended to treat fever in neonates. At recommended doses, paracetamol has not been associated with liver injury in neonates, while hepatotoxicity may occur after intake of a single high dose or multiple excessive doses. The aim of this narrative review is to critically analyze and summarize the available literature on newborns and infants exposed to supratherapeutic doses of paracetamol, with special focus on their clinical features, outcome, and management.MethodsThe PubMed, SCOPUS, and Google Scholar search engines were used to collect data, without time limitation. The following keywords were used: paracetamol/acetaminophen, overdose, hepatotoxicity, N-acetylcysteine, newborn, infant.ResultsThe literature search identified a total of 27 case reports, a number of review articles, and few other relevant publications. Neonatal poisoning from paracetamol resulted from transplacental drug transfer after maternal overdose in some published cases, while it was the consequence of medication errors in other cases. Newborns and infants who have received a single overdose and have paracetamol concentrations below the Rumack-Matthew nomogram limits are at low risk of serious hepatic damage, while those who have recently ingested more than one supratherapeutic dose of paracetamol should be managed with caution. The treatment of choice for paracetamol poisoning is N-acetylcysteine, a specific antidote which reduces paracetamol hepatotoxic effects. N-Acetylcysteine should be given according to specific regimens through weight-based dosing tables.ConclusionsCaution should be used when paracetamol is administered to the newborn. In the event of an overdose, careful patient monitoring and personalization of post-overdose procedures are recommended.

Oral drug bioavailability may be significantly altered after laparoscopic sleeve gastrectomy (LSG), the most popular bariatric procedure worldwide. Paracetamol (acetaminophen) is the post-bariatric analgesic/antipyretic drug of choice. In this work we studied and analyzed the LSG effects on systemic bioavailability and pharmacokinetics of paracetamol after oral administration of solid vs. liquid dosage form. A 4-armed, pharmacokinetic, crossover trial was performed in patients enrolled for LSG. Single paracetamol dose (500 mg), as caplet (n = 7) or syrup (n = 5), was administered before vs. 4–6 months post-LSG. Bioavailability was enhanced after LSG; in the caplet groups, average AUC0–t increased from 9.1 to 18.6 µg·h/mL with AUC0–t difference of 9.5 µg·h/mL (95% CI 4.6–14.5, p = 0.003). Cmax increased from 1.8 (95% CI 1.2–2.5) to 4.2 µg/mL (3.6–4.8) after LSG (p = 0.032). In the syrup groups, AUC0–t increased from 13.4 to 25.6 µg·h/mL, with AUC0–t difference of 12.2 µg·h/mL (95% CI 0.9–23.5, p = 0.049). Cmax changed from 5.4 (95% CI 2.5–8.4) to 7.8 µg/mL (6.1–9.6), and systemic bioavailability was complete (102%) after the surgery. Overall, decreased paracetamol exposure in obesity, with recovery to normal drug levels (caplet) or even higher (syrup) post-LSG, was revealed. In conclusion, attention to paracetamol effectiveness/safety in obesity, and after bariatric surgery, is prudent.

The occurrence of human as well as veterinary drug residues in surface water is caused by their insufficient removal ability from wastewater. Drug residues disturb the natural balance of water ecosystem, have a negative effect on non-target organisms and pose a significant risk for human health. The main aim of this study was to determine the concentration of residues of eight drugs from the group of sulfonamides (sulfathiazole, sulfadiazine, sulfamethazine, sulfamethoxazole, sulfadimethoxine, sulfadoxine, sulfamerazine, sulfachlorpyridazine), four drugs from the non-steroidal anti-inflammatory drug group (ibuprofen, ketoprofen, naproxen, diclofenac) and one representative of the analgesics-antipyretics group [paracetamol (acetaminophen)] in the surface water of the Elbe river basin. A total of 65 samples of surface water from the Elbe river basin were taken during August 2018 when the weather was constant without any significant fluctuations. The analysis was performed by means of liquid chromatography with tandem mass spectrometry (LC-MS/MS). The results have shown the numerous occurrences of sulfamethoxazole, ibuprofen, naproxen, diclofenac and paracetamol (acetaminophen). A statistically significant negative correlation between the river flow rate in the monitored locations and the residue concentration was found for ibuprofen, naproxen, diclofenac and paracetamol (acetaminophen). The most significant findings of the monitored drug residues were mostly determined in samples from small streams below larger urban settlements with a hospital or other health facilities.

Background The enlargement of the European Union since 2004 has led to an increase in the number of Eastern European migrants living in the UK. The health of this group is under-researched though some mixed evidence shows they are at higher risk of certain physical health conditions such as heart attacks, strokes, HIV and alcohol use and have poorer mental health. This is compounded by poor or insecure housing, low pay, isolation and prejudice. We aimed to understand the health needs and health service experiences of the Eastern European population in a town in Northern England. Methods Five semi structured one-to-one and small group interviews and five focus groups were conducted with 42 Eastern European participants between June and September 2014. The majority of participants were Polish and other participants were from Belarus, Hungary, Latvia, Russia, Slovakia and Ukraine. The data were analysed using thematic framework analysis. Results Key findings included a good understanding the UK health service structure and high registration and use of general practice/primary care services. However, overall, there were high levels of dissatisfaction, frustration and distrust in General Practitioners (GP). The majority of participants viewed the GP as unhelpful and dismissive; a barrier to secondary/acute care; reluctant to prescribe antibiotics; and that GPs too often advised them to take paracetamol (acetaminophen) and rest. Conclusions Overwhelmingly participants had strong opinions about access to primary care and the role of the general practitioners. Although the design of the UK health service was well understood, participants were unhappy with the system of GP as gatekeeper and felt it inferior to the consumer-focused health systems in their country of origin. More work is needed to promote the importance of self-care, reduce antibiotic and medication use, and to increase trust in the GP.

BackgroundOver-the-counter medications (OTC) are safe and effective when patients follow the patient’s information leaflet (PIL) instructions and/or the instructions given by healthcare professionals (HCPs). However, OTC medications could be harmful and unsafe when individuals do not follow the given instructions and/or when their understanding about the proper use of OTC medications is incorrect. This study aimed to investigate the knowledge and perceptions of people regarding paracetamol use in the Republic of Cyprus.MethodsThis cross-sectional study, which belongs to quantitative research methods, included participants visiting community pharmacies in the following three cities of the Republic of Cyprus: Nicosia, Limassol and Larnaca. Participation in the study was voluntary and anonymous. Participants responded to the survey-based questionnaire, which concerned their knowledge and views on paracetamol use. After the data collection, responses were tabulated and analysed statistically.ResultsThe original compound was shown to be more well-known compared to generics. A notable percentage of respondents—ranging between 13.0% (N = 49) and 29.8% (N = 112)—answered incorrectly that broadly used non-steroidal anti-inflammatory drugs (NSAIDs) contain paracetamol. Furthermore, a remarkable percentage of respondents (71.5%, N = 269 and 50.3%, N = 189, respectively) falsely believed that two widely used combination products in the market of Cyprus (Paracetamol and Hyoscine-N-butylbromide; Paracetamol and Codeine and Caffeine) did not contain paracetamol. A notable percentage of participants (27.6%, N = 100) believed that paracetamol causes low toxicity. More than a third of the respondents (40.2%, N = 149) drink alcohol together with or slightly after consuming paracetamol products. This viewpoint was linked with the participants’ attitude towards consuming paracetamol medications after drinking alcohol (OR for consuming alcohol versus not consuming alcohol 0.100, 95% CI 0.044–0.225, p = 0.000).ConclusionsTo the best of our knowledge, this is the first study conducted in the Republic of Cyprus on this topic. Paracetamol is frequently consumed by individuals, both in its generic and original forms. However, the study showed that respondents often misperceive NSAIDs and paracetamol-containing medications. In addition, it is identified that there is a lack of education among people about the safe and effective use of paracetamol, namely, indications, potential side effects, maximum daily dose, alcohol consumption, and the potential risks of hepatotoxicity. The study contributed to the current published literature as it showed that there is a significant public health issue, for which appropriate measures can be established by the respective Authorities of Cyprus.

On-line electrochemistry/liquid chromatography/mass spectrometry was used to simulate the detoxification mechanism of paracetamol in the body. In an electrochemical flow-through cell, paracetamol was oxidized at a porous glassy carbon working electrode at a potential of 600 mV vs. Pd/H₂ with formation of a quinoneimine intermediate. The quinoneimine further reacted with glutathione and/or N-acetylcysteine to form isomeric adducts via the thiol function. The adducts were characterized on-line by liquid chromatography/mass spectrometry. These reactions are similar to those occurring between paracetamol and glutathione under catalysis by cytochrome P450 enzymes in the body.