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Expert Opinion on Drug Metabolism &... Aug 2018Patent ductus arteriosus (PDA) persistence is associated, in prematures, to several complications. The optimal PDA management is still under debate, especially regarding... (Comparative Study)
Comparative Study Review
Patent ductus arteriosus (PDA) persistence is associated, in prematures, to several complications. The optimal PDA management is still under debate, especially regarding the best therapeutic approach and the time to treat. The available drugs are not exempt from contraindications and side effects; ibuprofen itself, although representing the first-choice therapy, can show nephrotoxicity and other complications. Paracetamol seems a valid alternative to classic nonsteroidal anti-inflammatory Drugs, with a lower toxicity. Areas covered: Through an analysis of the published literature on ibuprofen and paracetamol effects in preterm neonates, this review compares the available treatments for PDA, analyzing the mechanisms underlining ibuprofen-associated nephrotoxicity and the eventual paracetamol-induced hepatic damage, also providing an update of what has been yet demonstrated and a clear description of the still open issues. Expert Opinion: Paracetamol is an acceptable alternative in case of contraindication to ibuprofen; its toxicity, in this setting, is very low. Lower doses may be effective, with even fewer risks. In the future, paracetamol could represent an efficacious first-line therapy, although its safety, optimal dosage, and global impact have to be fully clarified through long-term trials, also in the perspective of an individualized and person-based therapy taking into account the extraordinary individual variability.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Ductus Arteriosus, Patent; Humans; Ibuprofen; Infant, Newborn; Infant, Premature
PubMed: 29938546
DOI: 10.1080/17425255.2018.1492550 -
Environmental Science and Pollution... Mar 2023This study investigated the possible protective role of mulberry leaf (MLE) and olive leaf (OLE) ethanolic extracts against paracetamol (PTL)-induced liver injury in...
The palliative effect of mulberry leaf and olive leaf ethanolic extracts on hepatic CYP2E1 and caspase-3 immunoexpression and oxidative damage induced by paracetamol in male rats.
This study investigated the possible protective role of mulberry leaf (MLE) and olive leaf (OLE) ethanolic extracts against paracetamol (PTL)-induced liver injury in rats compared to silymarin as a reference drug. Initially, MLE and OLE were characterized using gas chromatography-mass spectrometry (GC/MS). Then, forty male Sprague Dawley rats were divided into five groups: the negative control group orally received distilled water for 35 days, the PTL-treated group (PTG) received 500 mg PTL/kg b. wt. for 7 days, the MLE-treated group (MLTG) received 400 mg MLE/kg b. wt., the OLE-treated group (OLTG) received 400 mg OLE/kg b. wt., and the silymarin-treated group (STG) received 100 mg silymarin/kg b. wt. The last three groups received the treatment for 28 days, then PTL for 7 days. The GC-MS characterization revealed that MLE comprised 19 constituents dominated by ethyl linoleate, phytol, hexadecanoic acid, ethyl ester, and squalene. Moreover, OLE comprised 30 components, and the major components were 11-eicosenoic acid, oleic acid, phytol, and à-tetralone. MLE and OLE significantly corrected the PTL-induced normocytic normochromic anemia, leukocytosis, hypercholesterolemia, and hypoproteinemia. Moreover, the MLE and OLE pretreatment considerably suppressed the PTL-induced increment in serum levels of hepatic enzymes, including alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase. Furthermore, the PTL-induced depletion in antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and catalase, and the rise in hepatic malondialdehyde content were significantly reversed by the MLE and OLE pretreatment. Besides, MLE and OLE pretreatment significantly protected the hepatic tissue against PTL-induced DNA damage, pathological perturbations, and increased caspase 3 and CYP2E1 immunoexpression. Of note, OLTG showed better enhancement of most indices rather than MLTG. Conclusively, these findings imply that OLE, with its antioxidant and antiapoptotic capabilities, is superior to MLE in protecting against PTL-induced liver injury.
Topics: Rats; Male; Animals; Antioxidants; Acetaminophen; Morus; Olea; Caspase 3; Cytochrome P-450 CYP2E1; Rats, Sprague-Dawley; Chemical and Drug Induced Liver Injury, Chronic; Oxidative Stress; Liver; Silymarin; Plant Leaves; Plant Extracts; Chemical and Drug Induced Liver Injury
PubMed: 36637651
DOI: 10.1007/s11356-023-25152-z -
Australian Journal of General Practice Apr 2019Paracetamol is a widely used analgesic to which hypersensitivity reactions are rare. Reactions to paracetamol may be due to the pharmacological effects of...
BACKGROUND
Paracetamol is a widely used analgesic to which hypersensitivity reactions are rare. Reactions to paracetamol may be due to the pharmacological effects of cyclooxygenase-1 inhibition or, more rarely, due to a selective allergy against paracetamol.
OBJECTIVE
This article aims to review the current literature in the context of two cases seen in the authors' allergy practice.
DISCUSSION
Paracetamol allergy is uncommon and, as a result, may be overlooked as a cause for immediate hypersensitivity, which can lead to a significant delay in diagnosis. Currently, specialist referral for a supervised oral challenge is required for formal diagnosis.
Topics: Acetaminophen; Allergy and Immunology; Anti-Inflammatory Agents, Non-Steroidal; Drug Hypersensitivity; Humans; Referral and Consultation
PubMed: 31256492
DOI: 10.31128/AJGP-08-18-4689 -
Pharmacology Research & Perspectives Aug 2022Semaglutide is a glucagon-like-peptide-1 (GLP-1) analogue marketed for once-weekly subcutaneous administration for type 2 diabetes mellitus. Like other long-acting GLP-1...
Semaglutide is a glucagon-like-peptide-1 (GLP-1) analogue marketed for once-weekly subcutaneous administration for type 2 diabetes mellitus. Like other long-acting GLP-1 analogues, semaglutide reduces gastric emptying and, potentially, alters the rate of absorption of orally co-administered drugs. The objective of the current analysis was to evaluate the effects on the gastric emptying rate caused by semaglutide on pharmacokinetic model parameters of paracetamol and atorvastatin in healthy subjects. Non-linear mixed effect modeling was used to estimate population pharmacokinetic model parameters of paracetamol and atorvastatin after single doses with or without semaglutide. The absorption rate (ka) of paracetamol decreased by 53% when co-administered with semaglutide. For atorvastatin, ka and transit compartment rate (ktr) decreased by 72% and 91%, respectively. Thus, gastric emptying, measured as T50, i.e., drug disappearance from the absorption compartments, showed an additional 5-min delay for paracetamol and a 67-min delay for atorvastatin when co-administered with semaglutide. Semaglutide affected pharmacokinetic model parameters of paracetamol and atorvastatin, and minor quantitative differences in gastric emptying between placebo vs. semaglutide administration were observed. However, these effects of semaglutide were considered not to be of clinical relevance.
Topics: Acetaminophen; Atorvastatin; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Hypoglycemic Agents
PubMed: 35799471
DOI: 10.1002/prp2.962 -
Molecules (Basel, Switzerland) Mar 2022The analytical performance of the clay paste electrode and graphene paste electrode was compared using square wave voltammetry (SWV) and cyclic voltammetry (CV). The...
The analytical performance of the clay paste electrode and graphene paste electrode was compared using square wave voltammetry (SWV) and cyclic voltammetry (CV). The comparison was made on the basis of a paracetamol (PA) determination on both working electrodes. The influence of pH and SWV parameters was investigated. The linear concentration ranges were found to be 6.0 × 10-3.0 × 10 and 2.0 × 10-8.0 × 10 mol L for clay paste electrode (ClPE) and graphene paste electrode (GrPE), respectively. The detection and quantification limits were calculated as 1.4 × 10 and 4.7 ×10 mol L for ClPE and 3.7 × 10 and 1.2 × 10 mol L for GrPE, respectively. Developed methods were successfully applied to pharmaceutical formulations analyses. Scanning electron microscopy and energy-dispersive X-ray spectroscopy were used to characterize ClPE and GrPE surfaces. Clay composition was examined with wavelength dispersive X-ray (WDXRF).
Topics: Acetaminophen; Carbon; Clay; Electrochemical Techniques; Electrodes; Graphite
PubMed: 35408436
DOI: 10.3390/molecules27072037 -
Water Science and Technology : a... 2016Pharmaceutical residues released into the environment are posing more and more public health problems. It is worthwhile to study the retention of pharmaceuticals...
Pharmaceutical residues released into the environment are posing more and more public health problems. It is worthwhile to study the retention of pharmaceuticals residues by adsorption on solid supports. Batch sorption experiments are intended to identify the adsorption isotherms of the pharmaceutically active ingredient on the biomaterials. The results obtained in this study have shown that the retention possibilities of these compounds by bio-adsorbents (clay and sand) are not significant. The negligible sorption for these media is explained by the low hydrophobicity of paracetamol (Log K(ow) = 0.46). The retention of paracetamol on the dehydrated sewage sludge and on Posidonia oceanica showed a relatively significant adsorption with a maximal quantity of 0.956 mg g(-1) and 1.638 mg g(-1) for the dehydrate sludge and P. oceanica, respectively. On the other hand, the study of paracetamol retention on the powdered activated carbon showed a high adsorption capacity of about 515.27 mg g(-1). Isotherm data show a good fit with Langmuir's model. An infrared analysis is carried out. It shows identical bands before and after adsorption, with some modifications.
Topics: Acetaminophen; Adsorption; Alismatales; Aluminum Silicates; Biodegradation, Environmental; Charcoal; Clay; Environmental Restoration and Remediation; Geologic Sediments; Sewage
PubMed: 27387007
DOI: 10.2166/wst.2016.218 -
BMJ (Clinical Research Ed.) Dec 2019
Topics: Acetaminophen; Drug Overdose; Humans; Osteoarthritis, Knee; Pain; Practice Guidelines as Topic
PubMed: 31892511
DOI: 10.1136/bmj.l6693 -
International Archives of Allergy and... 2018Acetaminophen is the most commonly used antipyretic in children. However, there are limited data assessing hypersensitivity reactions related to acetaminophen usage. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acetaminophen is the most commonly used antipyretic in children. However, there are limited data assessing hypersensitivity reactions related to acetaminophen usage.
OBJECTIVES
To conduct a systematic review to characterize reported reactions to acetaminophen in adults and children, and perform a meta-analysis to assess the prevalence of acetaminophen hypersensitivity in children with a suspected acetaminophen allergy.
METHODS
We performed a systematic review of studies reporting hypersensitivity reactions to acetaminophen by searching 2 electronic databases. From the selected studies, we included those assessing the prevalence of acetaminophen hypersensitivity by performing oral challenge in our meta-analysis.
RESULTS
Eighty-five studies were included in the systematic review, assessing a total of 1,030 participants. Immediate (within 1 h of exposure) hypersensitivity reactions were reported in > 25% of the articles, while cutaneous nonimmediate reactions were similarly reported in about 25% of the articles. The remaining articles reported Steven-Johnson syndrome/toxic epidermal necrolysis, fixed drug eruptions, and cross-intolerance reactions. Five pediatric studies were included in our meta-analysis. The prevalence of acetaminophen hypersensitivity reaction among children undergoing oral challenge was 10.1% (95% confidence interval 4.5-15.5).
CONCLUSION
Future studies assessing the risk of immediate and nonimmediate hypersensitivity reactions to acetaminophen and elucidating the mechanism of acetaminophen hypersensitivity reactions are required.
Topics: Acetaminophen; Child; Drug Hypersensitivity; Humans; Male; Prevalence
PubMed: 29614487
DOI: 10.1159/000487556 -
The Cochrane Database of Systematic... Jun 2016Tension-type headache (TTH) affects about 1 person in 5 worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tension-type headache (TTH) affects about 1 person in 5 worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (two to 14 headaches per month), and chronic TTH (15 headache days a month or more). Paracetamol (acetaminophen) is one of a number of analgesics suggested for acute treatment of headaches in frequent episodic TTH.
OBJECTIVES
To assess the efficacy and safety of paracetamol for the acute treatment of frequent episodic TTH in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (CRSO), MEDLINE, EMBASE, and the Oxford Pain Relief Database to October 2015, and also reference lists of relevant published studies and reviews. We sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers' websites.
SELECTION CRITERIA
We included randomised, double-blind, placebo-controlled studies (parallel-group or cross-over) using oral paracetamol for symptomatic relief of an acute episode of TTH. Studies had to be prospective, with participants aged 18 years or over, and include at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion and extracted data. We used the numbers of participants achieving each outcome to calculate the risk ratio (RR) and number needed to treat for one additional beneficial outcome (NNT) or one additional harmful outcome (NNH) for oral paracetamol compared to placebo or an active intervention for a range of outcomes, predominantly those recommended by the International Headache Society (IHS).We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created 'Summary of findings' tables.
MAIN RESULTS
We included 23 studies, all of which enrolled adults with frequent episodic TTH. Twelve studies used the IHS diagnostic criteria or similar, six used the older classification of the Ad Hoc Committee, and five did not describe specific diagnostic criteria but generally excluded participants with migraines. Participants had moderate or severe pain at the start of treatment. While 8079 people with TTH participated in these studies, the numbers available for any analysis were lower than this because outcomes were inconsistently reported and because many participants received active comparators.None of the included studies were at low risk of bias across all domains considered, although for most studies and domains this was likely to be due to inadequate reporting rather than poor methods. We judged five studies to be at high risk of bias for incomplete outcome reporting, and seven due to small size.For the IHS preferred outcome of being pain free at two hours the NNT for paracetamol 1000 mg compared with placebo was 22 (95% confidence interval (CI) 15 to 40) in eight studies (5890 participants; high quality evidence), with no significant difference from placebo at one hour. The NNT was 10 (7.9 to 14) for pain-free or mild pain at two hours in five studies (5238 participants; high quality evidence). The use of rescue medication was lower with paracetamol 1000 mg than with placebo, with an NNTp to prevent an event of 7.8 (6.0 to 11) in six studies (1856 participants; moderate quality evidence). On limited data, the efficacy of paracetamol 500 mg to 650 mg was not superior to placebo, and paracetamol 1000 mg was not different from either ketoprofen 25 mg or ibuprofen 400 mg (low quality evidence).Adverse events were not different between paracetamol 1000 mg and placebo (RR 1.1 (0.94 to 1.3); 5605 participants; 11 studies; high quality evidence). Studies reported no serious adverse events.The quality of the evidence using GRADE comparing paracetamol 1000 mg with placebo was moderate to high. Where evidence was downgraded it was because a minority of studies reported the outcome. For comparisons of paracetamol 500 mg to 650 mg with placebo, and of paracetamol 1000 mg with active comparators, we downgraded the evidence to low quality or very low quality because of the small number of studies and events.
AUTHORS' CONCLUSIONS
Paracetamol 1000 mg provided a small benefit in terms of being pain free at two hours for people with frequent episodic TTH who have an acute headache of moderate or severe intensity.
Topics: Acetaminophen; Administration, Oral; Adult; Analgesics, Non-Narcotic; Humans; Pain Measurement; Randomized Controlled Trials as Topic; Tension-Type Headache; Time Factors
PubMed: 27306653
DOI: 10.1002/14651858.CD011889.pub2 -
British Journal of Clinical Pharmacology Nov 2015The antiviral agent favipiravir is likely to be co-prescribed with acetaminophen (paracetamol). The present study evaluated the possiblility of a pharmacokinetic...
AIMS
The antiviral agent favipiravir is likely to be co-prescribed with acetaminophen (paracetamol). The present study evaluated the possiblility of a pharmacokinetic interaction between favipiravir and acetaminophen, in vitro and in vivo.
METHODS
The effect of favipivir on the transformation of acetaminophen to its glucuronide and sulfate metabolites was studied using a pooled human hepatic S9 fraction in vitro. The effect of acute and extended adminstration of favipiravir on the pharmacokinetics of acetaminophen and metabolites was evaluated in human volunteers.
RESULTS
Favipiravir inhibited the in vitro formation of acetaminophen sulfate, but not acetaminophen glucuronide. In human volunteers, both acute (1 day) and extended (6 days) administration of favipiravir slightly but significantly increased (by about 20 %) systemic exposure to acetaminophen (total AUC), whereas Cmax was not significantly changed. AUC for acetaminophen glucuronide was increased by 23 to 35 % above control by favipiravir, while AUC for acetaminophen sulfate was reduced by about 20 % compared to control. Urinary excretion of acetaminophen sulfate was likewise reduced to 44 to 65 % of control values during favipiravir co-administration, while excretion of acetaminophen glucuronide increased to 17 to 32 % above control.
CONCLUSION
Favipiravir inhibits acetaminophen sulfate formation in vitro and in vivo. However the increase in systemic exposure to acetaminophen due to favipiravir co-administration, though statistically significant, is small in magnitude and unlikely to be of clinical importance.
Topics: Acetaminophen; Adult; Amides; Analgesics, Non-Narcotic; Antiviral Agents; Drug Interactions; Female; Humans; In Vitro Techniques; Inhibitory Concentration 50; Male; Middle Aged; Pyrazines; Young Adult
PubMed: 25808818
DOI: 10.1111/bcp.12644