Early bioavailability of paracetamol after oral or intravenous administration

Pettersson, Pia Holmér; Öwall, Anders; Jakobsson, Jan

doi:10.1111/j.0001-5172.2004.00452.x

Cited by 101 publications

(69 citation statements)

References 19 publications

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“…8) Oral administration of acetaminophen has been shown to be at least as effective as intravenous administration of an equivalent dose of acetaminophen, and the target concentration achieved more rapidly and with less variability in plasma concentrations compared with enteral formulations. 9,10) In the present investigation, there was no signs of behavioural changes were observed during the study period in all the treatment groups. Increase in body weights and growth of treated animals of either sex were of similar pattern as in control groups.…”

Section: Discussioncontrasting

confidence: 49%

Sub-acute Toxicity Studies of Acetaminophen in Sprague Dawley Rats

Deecaraman

Vijayalakshmi

et al. 2014

Biological & Pharmaceutical Bulletin

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The aim of the present study was to evaluate the sub-acute oral toxicity of acetaminophen in Sprague Dawley (SD) rats at 250 to 1000 mg/kg body weight (b.wt.). The following observations were noticed during the study. No mortality in male and female rats, at and up to the dose of 1000 mg/kg b.wt. There were abnormal clinical signs observed on female animals at 1000 mg/kg b.wt. dose level. There were no difference in body weight gain and no effect on the daily feed consumption. No toxicologically significant effect on the haematological parameters but liver and kidney related biochemical parameter showed significant difference at 1000 mg/kg b.wt. in females. No toxicologically significant effect on the urinalysis parameters, absolute and relative organ weights and gross pathological alterations; whereas histopathological alterations were observed in female liver at dose level of 1000 mg/kg b.wt. were observed. Based on the findings of this study, the No Observed Adverse Effect Level (NOAEL) of acetaminophen in SD rats, following oral administration at the doses of 250, 500 and 1000 mg/kg on daily basis was found to be 500 mg/kg b.wt.Key words acetaminophen; rat; hematology; biochemistry Acetaminophen (paracetamol) is a widely consumed antipyretic over-the-counter (OTC) drug in India in spite of it was banned in most of the developed countries. Acetaminophen was first evaluated for pharmacologic activity in 1893 by Von Mehring, who discovered its analgesic and antipyretic properties; however, it was not until the work of Brodie in the 1940's that serious consideration was given to its use in humans. 1)Acetaminophen was first introduced as a prescription drug in the United States in 1955 and was approved by the Food and Drug Administration for sale as a non prescription drug in 1960.2) Toxicity from acetaminophen is not from the drug itself but from one of its metabolites, N-acetyl-p-benzoquinoneimine (NAPQ1). Acetaminophen biotransformation involves conjugation with glucoronide and sulphate. A small amount of acetaminophen is metabolised by mixed function oxidase enzymes to form highly reactive compound NAPQ1, which is immediately conjugated with glutathione and subsequently excreted as cysteine and mercapturic conjugates. In overdoses, large amounts of acetaminophen are metabolised by oxidation because of saturation of the sulphate conjugation pathway, 3,4) but once the protective intracellular glutathione stores are depleted hepatic and renal damage may ensue. Hepatotoxicity is the most remarkable feature of acetaminophen overdose.5) Acute overdoses of acetaminophen can cause potentially fatal liver damage and, in rare individuals, a normal dose can do the same; the risk is heightened by alcohol consumption. Acetaminophen toxicity is the foremost cause of acute liver failure. Renal effects of acetaminophen overdose are less commonly seen than hepatic effects. However, renal impairment may be more common than previously recognised. There are extensive toxicity studies on acetaminophen are available. However, ther...

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Section: Discussioncontrasting

confidence: 49%

Sub-acute Toxicity Studies of Acetaminophen in Sprague Dawley Rats

Deecaraman

Vijayalakshmi

et al. 2014

Biological & Pharmaceutical Bulletin

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“…Furthermore, another study compared the bioavailability of paracetamol after oral and i.v. (propacetamol) administration [11]. Oral administration of paracetamol as part of multimodal pain management immediately postoperatively resulted in a huge and unpredictable variation in plasma concentration compared with the i.v.…”

Section: Introductionmentioning

confidence: 99%

“…Oral administration of paracetamol as part of multimodal pain management immediately postoperatively resulted in a huge and unpredictable variation in plasma concentration compared with the i.v. administration [11]. Predictability of serum concentrations, quick achievement of C max after administration, and a higher C max (with probably larger therapeutic effect [12,13]) compared with oral [9] or rectal [6] administration) could argue for use of the parenteral formulation of paracetamol.…”

Section: Introductionmentioning

confidence: 99%

Paracetamol for intravenous use in medium- and intensive care patients: pharmacokinetics and tolerance

Maat

Tijssen

Brüggemann

et al. 2010

Eur J Clin Pharmacol

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Purpose We studied the pharmacokinetics of paracetamol and determine the incidence of hypotension after intravenous administration in medium-(MCU) and intensive care (ICU) patients. Methods All patients on the ICU/MCU starting with paracetamol i.v. were included, yielding 38 patients. Blood samples were collected at predetermined time points to determine paracetamol serum concentration. The number of patients with a clinically relevant reduction in systolic blood pressure (SBP) and the number of patients that needed intervention to regain an acceptable blood pressure level were assessed. Results Overall, pharmacokinetic data were roughly comparable with earlier publications, but differences were noted in the subgroup ICU patients. Also, there was a trend to a larger peak serum concentration (p=0.052) and a significantly smaller volume of distribution (p=0.033) in MCU patients compared with ICU patients. Twenty-two percent (22%) and 33% of patients had a clinically relevant reduction in systolic blood pressure (SBP) 15 and 30 min after start of paracetamol infusion, respectively. In six patients (16%), an intervention was needed to correct blood pressure. Overall, SBP was significantly reduced at T=15 min and 30 min postinfusion (p<0.003 at both time points) when compared with SBP at the start of paracetamol infusion. Conclusions Further research on differences in paracetamol pharmacokinetics between ICU and MCU patients is warranted, as these differences might result in differences in efficacy. Furthermore, administration of paracetamol i.v. as potential cause of hypotension in the critically ill patient must not be overlooked.

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“…19 IV acetaminophen has been shown to achieve higher maximum concentrations and earlier time to maximum concentration compared to bioequivalent oral doses with less intrasubject variability. 15,16,[20][21][22] Mean maximum concentration after a standard 15-minute infusion of 1 g acetaminophen is approximately 70% higher than the mean maximum concentration observed at equivalent oral doses. 22 Peak CSF plasma concentrations of IV acetaminophen are 60% higher than with oral administration.…”

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confidence: 84%