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Serum pharmacokinetics of paracetamol. a -c: Concentrations of active paracetamol (APAP) and of glucuronide and N-sulfate metabolites were measured in serum after the intravenous administration of 1000 mg of paracetamol. Results are given separately for patients experiencing alleviations of fever or pain (indicated by Yes) and for patients not experiencing alleviations of fever or pain (indicated by No). P-values indicate differences between patients who experienced and patients who did not experience alleviations of their symptoms. NS: nonsignificant. d and e: scatterplots of changes of core temperature and of the visual analogue scale for pain (VAS) from the baseline to serum concentrations of the glucuronide metabolite at 1 h. Correlation coefficients, P-values, and the absolute number of observations for each correlation are provided.
Source publication
One prospective, open-label, non-randomized study was conducted in 100 patients to define the antipyretic and analgesic effect of a new intravenous formulation of 1 g of paracetamol; 71 received paracetamol for the management of fever and 29 received paracetamol for pain relief after abdominal surgery or for neoplastic pain. Serial follow-up measur...
Contexts in source publication
Context 1
... and of N-sulfate-APAP were measured in serum 1 h after the end of infusion and 6 h after the end of infusion. The clinical efficacy of paracetamol was correlated with its metabolism. Results showed that circulating concentrations of glucuronide-APAP after 1 h were greater in patients who failed to respond to paracetamol compared to responders (Fig. 5: a -c). To fully confirm these findings in individual patients, the correlations between serum levels of APAP and of both metabolites with changes of core temperature and of VAS from the baseline were explored. Results showed positive correlations between these changes and serum glucuronide-APAP at 1 h ( Fig. 5: d and e). No significant ...
Context 2
... paracetamol compared to responders (Fig. 5: a -c). To fully confirm these findings in individual patients, the correlations between serum levels of APAP and of both metabolites with changes of core temperature and of VAS from the baseline were explored. Results showed positive correlations between these changes and serum glucuronide-APAP at 1 h ( Fig. 5: d and e). No significant correlations were found between serum APAP and these changes (data not ...
Context 3
... parecetamol in some patients and the absence of any anti-inflammatory effect render more probable that the only factor that explains why some patients respond to paracetamol treatment more efficiently than others is the rate of metabolism. The positive correlations of the change of body temperature and of VAS with the glucuronide metabolite ( Fig. 5: d and e) suggest that a greater effort towards more rapid metabolism is done among non-responders compared to responders. The exact driver of this phenomenon remains to be ...
Citations
... [6][7][8][9] Research on adults suggests the administration of accessible intravenous paracetamol is more effective than oral paracetamol and well tolerated in patients with fever due to endotoxin, but limited data on the use of intravenous paracetamol in children. 10 In children, administration of intravenous paracetamol were also more effective than the administration of rectal paracetamol. There were much available data on its use as an antipyretic and analgesic in adult, but limited data on comparing the efficacy and tolerability of intravenous paracetamol compared to oral paracetamol as an antipyretic in febrile children. ...
... While temperature reduction in the oral group was increased as the concentration of plasma after oral administration increases with time, with large inter individual differences resulting in less predictable, especially at the first 80 minutes. 10 Normal temperatures in the intravenous group in this study was achieved faster than oral group as it decreased more rapidly. This effect can be predicted because of effect stability due to low variations of intravenous paracetamol bioavailability. ...
... It is used as an anti-pyretic widely, while its effect as analgesic has been a focus of consideration for many clinicians for a number of years. 9 Clinical practice necessitates investigating the methods which could effectively reduce the intensity of pain. Gabapentin has well known analgesic effects similar to paracetamol in different surgeries, but there is limited data to demonstrate its effects on hand surgery. ...
Objectives:
To compare the analgesic effects of gabapentin and paracetamol post-operatively in patients with hand injury.
Methods:
The double-blind, randomised control trial was conducted at the Department of Plastic Surgery, Dow University of Health Sciences, Karachi, from March to August 2019, and comprised subjects aged 18-60 years with hand injury who were randomly divided into group I which received gabapentin 600mg and group II which received paracetamol 1000 mg through anonymous packaging. Pain intensity was assessed using the visual analogue scale along with a self-designed questionnaire which was filled twice post-operatively; first at the time of drug intake once orally allowed; and thereafter six hours later. Data was analysed using SPSS 22.
Results:
Of the 50 subjects, there were 25(50%) in each of the two groups. Overall, there were 41(82%) males and 9(18%) females. The mean age of the total sample was 28.64±6.72 years. The most frequent side-effect reported in both groups was nausea; 11(44%) in group I and 9(36%) in group II. The least reported side-effect in group I was double vision 1(4%) which was not reported at all in group II and the least reported side-effect was dry mouth 1(4%). The analgesic effect between the groups were not significantly different (p>0.05).
Conclusions:
Both gabapentin and paracetamol were found to be effective in pain management, but the latter had slightly better pain control with relatively less side-effects.
Trial registration:
ClinicalTrials.gov Identifier: NCT04068506.
... However, the results report that subjects with no fever had a higher prevalence than fever. Different results were demonstrated by a study done a study in Athena, intravenous paracetamol group showed fever was 16 In our study oral paracetamol administration in this research reduced fever faster than intravenous paracetamol administration at the first 15 minutes. A study in 2008 reported that paracetamol dose 15 mg/kg reduced fever faster by 1 o C 30 minutes after oral paracetamol administration. ...
Background: The antipyretic effect of intravenous versus oral paracetamol is not well known. This study was aimed to compare the antipyretic effect of intravenous and oral paracetamol therapy to reduce fever.
Materials and Methods: This was an open-label randomized clinical trial study. The subjects were children who presented to Pediatric Ward and Emergency of Haji Adam Malik Hospital, aged from 2 months to 18 years old, with axillary temperature ≥38.0ºC. Subjects were divided into two groups, group 1 received 15 mg/kg paracetamol intravenous and group 2 received the same dose of paracetamol but given through intravenous. The temperature reduction was analyzed by ANOVA, and the change in temperature was recorded at 0, 15, 30, 60, 120, and 180 minutes after drug administration.
Results: In the first group, the mean temperature was decreased (p
... Acetaminophen (N-acetyl-para-amino-phenol, APAP) is the principal constituent of analgesic and cold medicines (Eccles, 2006;Jiang et al., 2014), and is an effective and widely used over-the-counter (OTC) analgesic-antipyretic in many countries (Goyal et al., 2012;Ji et al., 2012;Giamarellos-Bourboulis et al., 2014;Gupta and Jakobsson, 2014;Khoobi et al., 2014). ...
Acetaminophen (APAP) is an effective and widely used analgesic. However, APAP overdose is the principal cause of acute liver failure (ALF) in many countries. Here, we report the phenomenon of liver melanization which occurred before APAP-induced ALF in mice. A melanic surface induced by APAP which was time- and dose-dependent in the silkworm invertebrate model was observed. In addition, an APAP-induced acute tissue failure model (ATF) was established using a metabolic detoxification tissue fat body which simulated mouse liver. An investigation of the anabolic mechanism of melanin in experimental animals showed that dopaquinone and dopamine which were synthesized from tyrosine via dopa in silkworms were further metabolized to melanin, while in mice, epinephrine was synthesized via the dopamine branch and melanin was only synthesized via the dopaquinone branch. On this basis, it is proposed that melanin-metabolic levels in plasma could be used as an early diagnostic marker of APAP overdose and the black spots on insect epidermis could be used as a fast detection model of toxicity.
... Substituted acetanilides are known for their biological activity [1,2]. Some of them are effective analgesics [3,4]. These properties are a consequence of the structural peculiarities specific for this class of compounds. ...
Acetanilides are broadly used in the pharmaceutical industry. Thermochemical data on vapor pressures, solid-gas, liquid-gas, and solid-liquid phase transitions, as well as on enthalpies of formation of substituted acetanilides have been collected and evaluated with help of additional experimental measurements. Absolute vapor pressures of meta- and para-substituted acetanilides were studied by using transpiration method. Significant disagreement of available literature data on isomeric hydroxyacetanilides was detected and resolved. A quick estimation scheme of vaporization enthalpies of substituted acetanilides at 298.15 K was developed based on “structure-property” relationships. Quantum-chemical methods were applied for calculation of theoretical gas-phase enthalpies of formation of substituted acetanilides. Theoretical values together with results from “structure-property” analysis allowed for validation of the experimental crystalline state enthalpies of formation and prediction of these values based on quantum-chemical calculations.
... These studies found intravenous paracetamol to have a rapid antipyretic effect [15,16]. The only available publication on the antipyretic effect of intravenous paracetamol in infections described a population of 71 Greek patients enrolled in a prospective, open-label, single arm trial [17]. These patients were administered 1 g paracetamol intravenously within 15 min. ...
... These patients were administered 1 g paracetamol intravenously within 15 min. Defervescence was achieved in 73.2% of patients within 3 h [17]. ...
... Collected blood samples were centrifuged and serum was stored at -70°C. After thawing, concentrations of free paracetamol (APAP), glucuronide-APAP and N-sulfate-APAP were measured after analysis through a high-performance liquid chromatography system by an assay developed in-house, as described elsewhere [17]. ...
Aim:
No randomized study has been conducted for intravenous paracetamol (acetaminophen, APAP) for fever management due to infection. This is a study for a new ready-made infusion of paracetamol.
Methods:
80 patients with body temperature onset the last 24 hours greater than or equal to 38.5 °C due to infection were randomized to single administration of placebo (n = 39) or 1 g paracetamol (n = 41); temperature was recorded at standard intervals. Rescue medication with 1 g paracetamol was allowed. Serum samples were collected for measurement of APAP and metabolites. The primary endpoint was defervescence defined as core temperature below than or equal to 37.1 °C.
Results:
During the first six-hours, defervescence was achieved in 15 (38.5%) patients treated with placebo compared to 33 (80.5%) patients treated with paracetamol 1 g (p < 0.0001). Median time to defervescence with paracetamol 1 g was 3 hours. Rescue medication was given to 15 (38.5%) and five (12.2%) patients allocated to placebo and paracetamol respectively (p: 0.007); nine (60.0%) and two (40.0%) of these patients respectively experienced defervescence. No further antipyretic was needed for patients becoming afebrile with rescue medication. Serum glucuronide-APAP concentrations were significantly greater in the serum of patients who did not experience defervescence with paracetamol. The efficacy of paracetamol was not affected by serum creatinine. No study drug-related adverse events were reported.
Conclusions:
The 1 g paracetamol formulation has rapid and sustainable antipyretic effect for fever due to infection. Efficacy is dependent on hepatic metabolism.
The vapor pressures and enthalpies of sublimation/vaporization/fusion were determined for acetanilide and eight of its derivatives using fast scanning calorimetry (FSC, Flash DSC 1). The vapor pressures obtained made it possible to resolve the contradictions in the literature for 4′-hydroxyacetanilide (l/cr), 3′-hydroxyacetanilide (cr), and 4′-ethoxyacetanilide (l) and also confirmed the values obtained earlier for 4′-bromo-, 3′-bromo-, 4′-chloro-, and 3′-chloro-acetanilides. The vapor pressures were obtained for the first time for 3′-hydroxyacetanilide in the liquid state and 4′-nitroacetanilide in the crystalline state. The sublimation and vaporization enthalpies were determined using the obtained vapor pressures. In most cases, the enthalpies coincide, within the stated uncertainties, with the weighted average values calculated from the literature data. If the deviations were larger than the uncertainties, reasonable explanations were found. The fusion enthalpies of 4′-ethoxyacetanilide, 3′-hydroxyacetanilide, and 4′-hydroxyacetanilide were determined in two ways: through the fusion peak integration and by using the differences between sublimation and vaporization enthalpies. The enthalpies coincide within the error with the weighted average values calculated from the literature data.
Background
Glutathione S-transferase A1 (GSTA1) is a detoxification enzyme and a sensitive marker for hepatotoxicity. We investigated the effects of JNK inhibition on different degrees of Acetaminophen (APAP)-induced hepatocyte injury and GSTA1 expression.Objective
This study aimed to investigate the role of JNK signaling pathway in APAP-induced different degrees of hepatocyte injury and its correlation with GSTA1 by inhibiting the phosphorylation of JNK by SP600125.Results6 and 8 mM APAP induced different degrees of hepatocyte injury and apoptosis, both activated JNK signaling pathway. In contrast, JNK inhibitor significantly reduced activation of JNK and c-JUN on exposure to APAP. Meanwhile, the levels of hepatocyte injury, oxidative stress, and apoptosis obviously decreased. Importantly, GSTA1 expression was significantly increased by JNK inhibition.ConclusionsJNK inhibition attenuates APAP-induced hepatocyte injury and oxidative stress and increases GSTA1 expression. Furthermore, GSTA1 may be involved in this signaling pathway for detoxification.
This study reports a new stability indicating HPLC method using Spursil C18 column as stationary phase, and mixture of 0.1 M Na2HPO4 and methanol (50:50 v/v) as mobile phase for the chromatographic determination of paracetamol and prochlorperazine in tablets and in bulk form. The linearity range is 250-750 μg/mL for paracetamol and 2.5-7.5 μg/mL for prochlorperazine. The limit of detection values are 2.650 μg/mL for paracetamol and 0.175 μg/mL for prochlorperazine. The minor values of the relative standard deviation (≤ 2.0 %) as well as good percent assay values (nearer to 100 %) confirm the high precision and accuracy of the present method. From the degradation study chromatograms found that there was no interference from degradants when paracetamol and prochlorperazine are quantified in tablets through the proposed method. A good agreement between results obtained and labeled claim for the determination of paracetamol and prochlorperazine in tablet samples demonstrates that the proposed method is appropriate to quantify paracetamol and prochlorperazine in tablet formulations.
