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Molecules (Basel, Switzerland) Aug 2021Herein, we review the recent progress in the synthesis of representative nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen and naproxen. Although these drugs were... (Review)
Review
Herein, we review the recent progress in the synthesis of representative nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen and naproxen. Although these drugs were discovered over 50 years ago, novel practical and asymmetric approaches are still being developed for their synthesis. In addition, this endeavor has enabled access to more potent and selective derivatives from the key frameworks of ibuprofen and naproxen. The development of a synthetic route to ibuprofen and naproxen over the last 10 years is summarized, including developing methodologies, finding novel synthetic routes, and applying continuous-flow chemistry.
Topics: Electrochemistry; Humans; Hydrogenation; Ibuprofen; Naproxen; Oxidation-Reduction; Stereoisomerism
PubMed: 34443379
DOI: 10.3390/molecules26164792 -
JAMA Network Open Oct 2020Acetaminophen (paracetamol) and ibuprofen are the most widely prescribed and available over-the-counter medications for management of fever and pain in children. Despite... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Acetaminophen (paracetamol) and ibuprofen are the most widely prescribed and available over-the-counter medications for management of fever and pain in children. Despite the common use of these medications, treatment recommendations for young children remain divergent.
OBJECTIVE
To compare acetaminophen with ibuprofen for the short-term treatment of fever or pain in children younger than 2 years.
DATA SOURCES
Systematic search of the databases MEDLINE, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials and the trial registers ClinicalTrials.gov and the Australian New Zealand Clinical Trials Registry from inception to March 2019, with no language limits.
STUDY SELECTION
Studies of any design that included children younger than 2 years and directly compared acetaminophen with ibuprofen, reporting antipyretic, analgesic, and/or safety outcomes were considered. There were no limits on length of follow-up.
DATA EXTRACTION AND SYNTHESIS
Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline, 2 authors independently extracted data and assessed quality. Data were pooled using a fixed-effects method if I2 was less than 50% and using a random-effects method if I2 was 50% or greater.
MAIN OUTCOMES AND MEASURES
The primary outcomes were fever or pain within 4 hours of treatment onset. Safety outcomes included serious adverse events, kidney impairment, gastrointestinal bleeding, hepatotoxicity, severe soft tissue infection, empyema, and asthma and/or wheeze.
RESULTS
Overall, 19 studies (11 randomized; 8 nonrandomized) of 241 138 participants from 7 countries and various health care settings (hospital-based and community-based) were included. Compared with acetaminophen, ibuprofen resulted in reduced temperature at less than 4 hours (4 studies with 435 participants; standardized mean difference [SMD], 0.38; 95% CI, 0.08-0.67; P = .01; I2 = 49%; moderate quality evidence) and at 4 to 24 hours (5 studies with 879 participants; SMD, 0.24; 95% CI, 0.03-0.45; P = .03; I2 = 57%; moderate-quality evidence) and less pain at 4 to 24 hours (2 studies with 535 participants; SMD, 0.20; 95% CI, 0.03-0.37; P = .02; I2 = 25%; moderate-quality evidence). Adverse events were uncommon. Acetaminophen and ibuprofen appeared to have similar serious adverse event profiles (7 studies with 27 932 participants; ibuprofen vs aceteminophen: odds ratio, 1.08; 95% CI, 0.87-1.33; P = .50, I2 = 0%; moderate-quality evidence).
CONCLUSIONS AND RELEVANCE
In this study, use of ibuprofen vs acetaminophen for the treatment of fever or pain in children younger than 2 years was associated with reduced temperature and less pain within the first 24 hours of treatment, with equivalent safety.
Topics: Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Child, Preschool; Female; Fever; Humans; Ibuprofen; Infant; Male; Pain
PubMed: 33125495
DOI: 10.1001/jamanetworkopen.2020.22398 -
Molecules (Basel, Switzerland) Feb 2023The anti-inflammatory drug ibuprofen is considered to be an emerging contaminant because of its presence in different environments (from water bodies to soils) at... (Review)
Review
The anti-inflammatory drug ibuprofen is considered to be an emerging contaminant because of its presence in different environments (from water bodies to soils) at concentrations with adverse effects on aquatic organisms due to cytotoxic and genotoxic damage, high oxidative cell stress, and detrimental effects on growth, reproduction, and behavior. Because of its high human consumption rate and low environmental degradation rate, ibuprofen represents an emerging environmental problem. Ibuprofen enters the environment from different sources and accumulates in natural environmental matrices. The problem of drugs, particularly ibuprofen, as contaminants is complicated because few strategies consider them or apply successful technologies to remove them in a controlled and efficient manner. In several countries, ibuprofen's entry into the environment is an unattended contamination problem. It is a concern for our environmental health system that requires more attention. Due to its physicochemical characteristics, ibuprofen degradation is difficult in the environment or by microorganisms. There are experimental studies that are currently focused on the problem of drugs as potential environmental contaminants. However, these studies are insufficient to address this ecological issue worldwide. This review focuses on deepening and updating the information concerning ibuprofen as a potential emerging environmental contaminant and the potential for using bacteria for its biodegradation as an alternative technology.
Topics: Humans; Ibuprofen; Bacteria; Biodegradation, Environmental; Drug-Related Side Effects and Adverse Reactions; Technology; Water Pollutants, Chemical
PubMed: 36903343
DOI: 10.3390/molecules28052097 -
Ibuprofen in the treatment of children's inflammatory pain: a clinical and pharmacological overview.Minerva Pediatrica Feb 2019Unlike fever, which is often over-treated especially in children, pain is underestimated and under-treated in pediatric age. The pharmacological agents approved for... (Review)
Review
Unlike fever, which is often over-treated especially in children, pain is underestimated and under-treated in pediatric age. The pharmacological agents approved for treating pain in these patients are few, also considering the recent limitation for codeine in children younger than 12 years. Paracetamol and the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen are the most used at this purpose. The aim of this overview was to analyze the therapeutic appropriateness of ibuprofen in children based on its pharmacological properties. This work is a critical review of the pediatric literature over the last 20 years on efficacy and adverse events associated with the use of ibuprofen as analgesic in the pediatric population. Ibuprofen resulted effective in several pain conditions in children such as musculoskeletal pain, ear pain and acute otitis media, toothache and the inflammatory disease of the oral cavity and pharynx. The drug is a reasonable and efficacious alternative in postoperative pain, including tonsillectomy and adenoidectomy. It remains the treatment of choice for pain in chronic inflammatory diseases such as arthritis. Side effects and adverse events associated with ibuprofen are mild. It has the lowest gastrointestinal (GI) toxicity among NSAIDs, although some cases of GI toxicity may occur. Its renal effects are minimal, but dehydration plays an important role in triggering renal damage, so ibuprofen should not be given to patients with vomiting and diarrhea. Ibuprofen showed a good safety profile and provided evidence of effectiveness for mild-moderate pain of different origin in children. In case of fever or pain, the choice about the drug to be used should fall on ibuprofen in a clinical context where there is an inflammatory pathogenesis.
Topics: Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Child; Humans; Ibuprofen; Inflammation; Pain; Pain, Postoperative; Treatment Outcome
PubMed: 30574736
DOI: 10.23736/S0026-4946.18.05453-1 -
The Pan African Medical Journal 2020fever is the primary symptom of most childhood illnesses and a cause of concern to their caregivers. The antipyretics commonly used to treat fever are ibuprofen and... (Comparative Study)
Comparative Study Randomized Controlled Trial
INTRODUCTION
fever is the primary symptom of most childhood illnesses and a cause of concern to their caregivers. The antipyretics commonly used to treat fever are ibuprofen and paracetamol. Most studies on the effectiveness of ibuprofen and paracetamol in treating fever in under-fives were conducted in Europe and North America with very few in African children. This study was aimed at assessing the effectiveness and safety of a single dose therapy of ibuprofen versus paracetamol for treating childhood fever in Nigeria.
METHODS
a randomized, controlled clinical trial was conducted in the University of Calabar Teaching Hospital, in Nigeria. A total of 140 eligible children aged 6-59 months with tympanic temperature of 38°C-40°C were enrolled, and 70 of them were assigned to one arm that received a single dose of ibuprofen (10mg/kg) and 70 had paracetamol (15mg/kg). After drug administration, the children were admitted and observed in the hospital for six hours during which period a half-hourly temperature measurement and monitoring for adverse events were done.
RESULTS
the overall result showed that ibuprofen had a better fever reducing effect compared to paracetamol. The proportion of afebrile children in the ibuprofen versus paracetamol group at 1.5-2.5 hours of administration of the drugs was statistically significant (p = 0.04). The adverse events of both drugs were mild and quite comparable with vomiting being the commonest.
CONCLUSION
ibuprofen is more effective in the treating fever in under-fives compared to paracetamol. The adverse events of both drugs were mild and comparable.
Topics: Acetaminophen; Antipyretics; Body Temperature; Child, Preschool; Female; Fever; Hospitals, Teaching; Humans; Ibuprofen; Infant; Male; Nigeria; Vomiting
PubMed: 33224416
DOI: 10.11604/pamj.2020.36.350.21393 -
Italian Journal of Pediatrics Mar 2023Acute pain is a common symptom in children of all ages, and is associated with a variety of conditions. Despite the availability of guidelines, pain often remains...
BACKGROUND
Acute pain is a common symptom in children of all ages, and is associated with a variety of conditions. Despite the availability of guidelines, pain often remains underestimated and undertreated. Paracetamol and ibuprofen are the most commonly used drugs for analgesia in Pediatrics. Multimodal pain management by using a combination of paracetamol and ibuprofen results in greater analgesia.
METHODS
An investigation using the Nominal Group Technique was carried out between May and August 2022. Two open (non-anonymous) questionnaires were consecutively sent to a Board of ten clinicians to understand their opinions on the use of the oral paracetamol and ibuprofen association. Answers were examined in a final meeting where conclusions were drawn.
RESULTS
The board achieved a final consensus on a better analgesic power of paracetamol and ibuprofen in fixed-dose combination as compared to monotherapy, without compromising safety. Strong consensus was reached on the opinion that the fixed-dose combination of paracetamol and ibuprofen may be a useful option in case of inefficacy of one or other drug as monotherapy, especially in case of headaches, odontalgia, earache, and musculoskeletal pain. The use of the fixed combination may be also considered suitable for postoperative pain management.
CONCLUSIONS
The use of the fixed-dose combination may represent advantage in terms of efficacy and safety, allowing a better control of the dose of both paracetamol and ibuprofen as monotherapy, thus minimizing the risk of incorrect dosage. However, the limited evidence available highlights the need for future well designed studies to better define the advantages of this formulation in the various therapeutic areas.
Topics: Child; Humans; Acetaminophen; Acute Pain; Analgesics, Non-Narcotic; Consensus; Drug Combinations; Ibuprofen; Pain, Postoperative; Pain Management; Health Care Surveys; Administration, Oral
PubMed: 36945023
DOI: 10.1186/s13052-023-01445-4 -
Clinical Drug Investigation Oct 2015Previously published studies have suggested the lack of a pharmacokinetic interaction between ibuprofen and paracetamol when they are delivered as a fixed-dose oral... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
Previously published studies have suggested the lack of a pharmacokinetic interaction between ibuprofen and paracetamol when they are delivered as a fixed-dose oral combination. The aim of this study was to determine the pharmacokinetic profile and safety of a fixed-dose intravenous (IV) combination, containing 3 mg/mL ibuprofen and 10 mg/mL paracetamol, in comparison with its individual components. The study also assessed the relative bioavailability of the same doses of the active ingredients when they were administered as an oral formulation.
METHODS
A single-dose, open-label, randomized, five-period cross-over sequence pharmacokinetic study was undertaken in 30 healthy volunteers. Serial plasma samples were assayed for both paracetamol and ibuprofen concentrations, using validated liquid chromatography-tandem mass spectrometry methods. Pharmacokinetic parameters were computed using standard non-compartmental analyses. Adverse events were also assessed. The ratios of the maximum measured plasma concentration (C max), the area under the plasma concentration-time curve (AUC) from time zero to the time of the last measurable plasma concentration (AUCt ) and AUC from time zero to infinity (AUC∞) were analysed for bioequivalence as determined by 90% confidence intervals.
RESULTS
The pharmacokinetic parameters of ibuprofen and paracetamol were very similar for the combination and monotherapy IV preparations; the ratios of the C max, AUC t and AUC∞ values fell within the 80-125% acceptable bioequivalence range. Precise dose proportionality for both compounds was also determined for the half dose of the IV formulation in comparison with the full dose. The relative bioavailability of paracetamol (93.78%) and ibuprofen (96.45%) confirmed the pharmacokinetic equivalence of the oral and IV formulations of the fixed-dose combination.
CONCLUSION
Concomitant administration of 3 mg/mL ibuprofen and 10 mg/mL paracetamol in a fixed-dose IV combination does not alter the pharmacokinetic profiles of either drug. The IV and oral dose forms of such a combination are pharmacokinetically equivalent.
Topics: Acetaminophen; Administration, Intravenous; Administration, Oral; Adolescent; Adult; Area Under Curve; Biological Availability; Cross-Over Studies; Drug Combinations; Female; Healthy Volunteers; Humans; Ibuprofen; Male; Middle Aged; Therapeutic Equivalency; Young Adult
PubMed: 26334726
DOI: 10.1007/s40261-015-0320-8 -
Respiratory Research Feb 2023Ibuprofen is a nonsteroidal anti-inflammatory drug that is commonly used to stimulate closure of a patent ductus arteriosus (PDA) in very premature infants and may lead...
BACKGROUND
Ibuprofen is a nonsteroidal anti-inflammatory drug that is commonly used to stimulate closure of a patent ductus arteriosus (PDA) in very premature infants and may lead to aberrant neonatal lung development and bronchopulmonary dysplasia (BPD).
METHODS
We investigated the effect of ibuprofen on angiogenesis in human umbilical cord vein endothelial cells (HUVECs) and the therapeutic potential of daily treatment with 50 mg/kg of ibuprofen injected subcutaneously in neonatal Wistar rat pups with severe hyperoxia-induced experimental BPD. Parameters investigated included growth, survival, lung histopathology and mRNA expression.
RESULTS
Ibuprofen inhibited angiogenesis in HUVECs, as shown by reduced tube formation, migration and cell proliferation via inhibition of the cell cycle S-phase and promotion of apoptosis. Treatment of newborn rat pups with ibuprofen reduced pulmonary vessel density in the developing lung, but also attenuated experimental BPD by reducing lung inflammation, alveolar enlargement, alveolar septum thickness and small arteriolar wall thickening.
CONCLUSIONS
In conclusion, ibuprofen has dual effects on lung development: adverse effects on angiogenesis and beneficial effects on alveolarization and inflammation. Therefore, extrapolation of the beneficial effects of ibuprofen to premature infants with BPD should be done with extreme caution.
Topics: Infant, Newborn; Animals; Rats; Humans; Ibuprofen; Endothelial Cells; Animals, Newborn; Rats, Wistar; Lung; Bronchopulmonary Dysplasia; Hyperoxia
PubMed: 36732726
DOI: 10.1186/s12931-023-02342-4 -
Clinical Interventions in Aging 2014To determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement. (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
To determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement.
METHODS
367 primary knee osteoarthritis patients with a pain score of 5 or higher were randomized to receive ibuprofen 1,200 mg/day or C. domestica extracts 1,500 mg/day for 4 weeks. The main outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total, WOMAC pain, WOMAC stiffness, and WOMAC function scores. Adverse events (AEs) were also recorded.
RESULTS
185 and 182 patients were randomly assigned into C. domestica extracts and ibuprofen groups, respectively. The baseline characteristics were no different between groups. The mean of all WOMAC scores at weeks 0, 2, and 4 showed significant improvement when compared with the baseline in both groups. After using the noninferiority test, the mean difference (95% confidence interval) of WOMAC total, WOMAC pain, and WOMAC function scores at week 4 adjusted by values at week 0 of C. domestica extracts were noninferior to those for the ibuprofen group (P=0.010, P=0.018, and P=0.010, respectively), except for the WOMAC stiffness subscale, which showed a trend toward significance (P=0.060). The number of patients who developed AEs was no different between groups. However, the number of events of abdominal pain/discomfort was significantly higher in the ibuprofen group than that in the C. domestica extracts group (P=0.046). Most subjects (96%-97%) were satisfied with the treatment, and two-thirds rated themselves as improved in a global assessment.
CONCLUSION
C. domestica extracts are as effective as ibuprofen for the treatment of knee osteoarthritis. The side effect profile was similar but with fewer gastrointestinal AE reports in the C. domestica extracts group.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Curcuma; Female; Humans; Ibuprofen; Male; Middle Aged; Osteoarthritis, Knee; Phytotherapy; Plant Extracts; Treatment Outcome
PubMed: 24672232
DOI: 10.2147/CIA.S58535 -
The Cochrane Database of Systematic... Feb 2020Indomethacin is used as standard therapy to close a patent ductus arteriosus (PDA) but is associated with reduced blood flow to several organs. Ibuprofen, another... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Indomethacin is used as standard therapy to close a patent ductus arteriosus (PDA) but is associated with reduced blood flow to several organs. Ibuprofen, another cyclo-oxygenase inhibitor, may be as effective as indomethacin with fewer adverse effects.
OBJECTIVES
To determine the effectiveness and safety of ibuprofen compared with indomethacin, other cyclo-oxygenase inhibitor(s), placebo, or no intervention for closing a patent ductus arteriosus in preterm, low-birth-weight, or preterm and low-birth-weight infants.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 10), MEDLINE via PubMed (1966 to 30 November 2017), Embase (1980 to 30 November 2017), and CINAHL (1982 to 30 November 2017). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials of ibuprofen for the treatment of a PDA in preterm, low birth weight, or both preterm and low-birth-weight newborn infants.
DATA COLLECTION AND ANALYSIS
Data collection and analysis conformed to the methods of the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of evidence.
MAIN RESULTS
We included 39 studies enrolling 2843 infants. Ibuprofen (IV) versus placebo: IV Ibuprofen (3 doses) reduced the failure to close a PDA compared with placebo (typical relative risk (RR); 0.62 (95% CI 0.44 to 0.86); typical risk difference (RD); -0.18 (95% CI -0.30 to -0.06); NNTB 6 (95% CI 3 to 17); I = 65% for RR and I = 0% for RD; 2 studies, 206 infants; moderate-quality the evidence). One study reported decreased failure to close a PDA after single or three doses of oral ibuprofen compared with placebo (64 infants; RR 0.26, 95% CI 0.11 to 0.62; RD -0.44, 95% CI -0.65 to -0.23; NNTB 2, 95% CI 2 to 4; I test not applicable). Ibuprofen (IV or oral) compared with indomethacin (IV or oral): Twenty-four studies (1590 infants) comparing ibuprofen (IV or oral) with indomethacin (IV or oral) found no significant differences in failure rates for PDA closure (typical RR 1.07, 95% CI 0.92 to 1.24; typical RD 0.02, 95% CI -0.02 to 0.06; I = 0% for both RR and RD; moderate-quality evidence). A reduction in NEC (necrotising enterocolitis) was noted in the ibuprofen (IV or oral) group (18 studies, 1292 infants; typical RR 0.68, 95% CI 0.49 to 0.94; typical RD -0.04, 95% CI -0.07 to -0.01; NNTB 25, 95% CI 14 to 100; I = 0% for both RR and RD; moderate-quality evidence). There was a statistically significant reduction in the proportion of infants with oliguria in the ibuprofen group (6 studies, 576 infants; typical RR 0.28, 95% CI 0.14 to 0.54; typical RD -0.09, 95% CI -0.14 to -0.05; NNTB 11, 95% CI 7 to 20; I = 24% for RR and I = 69% for RD; moderate-quality evidence). The serum/plasma creatinine levels 72 hours after initiation of treatment were statistically significantly lower in the ibuprofen group (11 studies, 918 infants; MD -8.12 µmol/L, 95% CI -10.81 to -5.43). For this comparison, there was high between-study heterogeneity (I = 83%) and low-quality evidence. Ibuprofen (oral) compared with indomethacin (IV or oral): Eight studies (272 infants) reported on failure rates for PDA closure in a subgroup of the above studies comparing oral ibuprofen with indomethacin (IV or oral). There was no significant difference between the groups (typical RR 0.96, 95% CI 0.73 to 1.27; typical RD -0.01, 95% CI -0.12 to 0.09; I = 0% for both RR and RD). The risk of NEC was reduced with oral ibuprofen compared with indomethacin (IV or oral) (7 studies, 249 infants; typical RR 0.41, 95% CI 0.23 to 0.73; typical RD -0.13, 95% CI -0.22 to -0.05; NNTB 8, 95% CI 5 to 20; I = 0% for both RR and RD). There was low-quality evidence for these two outcomes. There was a decreased risk of failure to close a PDA with oral ibuprofen compared with IV ibuprofen (5 studies, 406 infants; typical RR 0.38, 95% CI 0.26 to 0.56; typical RD -0.22, 95% CI -0.31 to -0.14; NNTB 5, 95% CI 3 to 7; moderate-quality evidence). There was a decreased risk of failure to close a PDA with high-dose versus standard-dose of IV ibuprofen (3 studies 190 infants; typical RR 0.37, 95% CI 0.22 to 0.61; typical RD - 0.26, 95% CI -0.38 to -0.15; NNTB 4, 95% CI 3 to 7); I = 4% for RR and 0% for RD); moderate-quality evidence). Early versus expectant administration of IV ibuprofen, echocardiographically-guided IV ibuprofen treatment versus standard IV ibuprofen treatment, continuous infusion of ibuprofen versus intermittent boluses of ibuprofen, and rectal ibuprofen versus oral ibuprofen were studied in too few trials to allow for precise estimates of any clinical outcomes.
AUTHORS' CONCLUSIONS
Ibuprofen is as effective as indomethacin in closing a PDA. Ibuprofen reduces the risk of NEC and transient renal insufficiency. Therefore, of these two drugs, ibuprofen appears to be the drug of choice. The effectiveness of ibuprofen versus paracetamol is assessed in a separate review. Oro-gastric administration of ibuprofen appears as effective as IV administration. To make further recommendations, studies are needed to assess the effectiveness of high-dose versus standard-dose ibuprofen, early versus expectant administration of ibuprofen, echocardiographically-guided versus standard IV ibuprofen, and continuous infusion versus intermittent boluses of ibuprofen. Studies are lacking evaluating the effect of ibuprofen on longer-term outcomes in infants with PDA.
Topics: Cyclooxygenase Inhibitors; Ductus Arteriosus, Patent; Enzyme Inhibitors; Humans; Ibuprofen; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Randomized Controlled Trials as Topic
PubMed: 32045960
DOI: 10.1002/14651858.CD003481.pub8