Single dose bioavailability of acetaminophen following oral administration

Borin, Marie T.; Ayres, James W.

doi:10.1016/0378-5173(89)90097-5

Cited by 26 publications

(15 citation statements)

References 18 publications

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“…Adding the typical value of the lag phase (5 minutes) gives a time to 50% of gastric emptying of 10 minutes, which is within the reported range. In addition, acetaminophen bioavailability has previously been reported to be saturable in the same range as the semimechanistic model suggests (63%‐89%) …”

Section: Discussionmentioning

confidence: 76%

Semimechanistic model describing gastric emptying and glucose absorption in healthy subjects and patients with type 2 diabetes

Alskär

Røge

Knop

et al. 2015

The Journal of Clinical Pharma

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The integrated glucose-insulin (IGI) model is a previously published semimechanistic model that describes plasma glucose and insulin concentrations after glucose challenges. The aim of this work was to use knowledge of physiology to improve the IGI model's description of glucose absorption and gastric emptying after tests with varying glucose doses. The developed model's performance was compared to empirical models. To develop our model, data from oral and intravenous glucose challenges in patients with type 2 diabetes and healthy control subjects were used together with present knowledge of small intestinal transit time, glucose inhibition of gastric emptying, and saturable absorption of glucose over the epithelium to improve the description of gastric emptying and glucose absorption in the IGI model. Duodenal glucose was found to inhibit gastric emptying. The performance of the saturable glucose absorption was superior to linear absorption regardless of the gastric emptying model applied. The semiphysiological model developed performed better than previously published empirical models and allows better understanding of the mechanisms underlying glucose absorption. In conclusion, our new model provides a better description and improves the understanding of dynamic glucose tests involving oral glucose.

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Section: Discussionmentioning

confidence: 76%

Semimechanistic model describing gastric emptying and glucose absorption in healthy subjects and patients with type 2 diabetes

Alskär

Røge

Knop

et al. 2015

The Journal of Clinical Pharma

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“…Paracetamol is subjected to a first-pass metabolism, with hepatic extraction ratio of 0.11-0.37 in adults (30); so, the oral bioavailability is 60-89% (178); and the absorption half-life is 4.5 min with no lag time (7) [a lag time of 4.2 min has been reported in children (222)]. …”

Section: Pharmacokineticsmentioning

confidence: 99%

Paracetamol: New Vistas of an Old Drug

et al. 2006

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Paracetamol (acetaminophen) is one of the most popular and widely used drugs for the treatment of pain and fever. It occupies a unique position among analgesic drugs. Unlike NSAIDs it is almost unanimously considered to have no antiinflammatory activity and does not produce gastrointestinal damage or untoward cardiorenal effects. Unlike opiates it is almost ineffective in intense pain and has no depressant effect on respiration. Although paracetamol has been used clinically for more than a century, its mode of action has been a mystery until about one year ago, when two independent groups (Zygmunt and colleagues and Bertolini and colleagues) produced experimental data unequivocally demonstrating that the analgesic effect of paracetamol is due to the indirect activation of cannabinoid CB 1 receptors. In brain and spinal cord, paracetamol, following deacetylation to its primary amine (p-aminophenol), is conjugated with arachidonic acid to form N-arachidonoylphenolamine, a compound already known (AM404) as an endogenous cannabinoid. The involved enzyme is fatty acid amide hydrolase. N-arachidonoylphenolamine is an agonist at TRPV1 receptors and an inhibitor of cellular anandamide uptake, which leads to increased levels of endogenous cannabinoids; moreover, it inhibits cyclooxygenases in the brain, albeit at concentrations that are probably not attainable with analgesic doses of paracetamol. CB 1 receptor antagonist, at a dose level that completely prevents the analgesic activity of a selective CB 1 receptor agonist, completely prevents the analgesic ac- 250CNS Drug Reviews Vol. 12, No. 3-4, pp. 250-275 © 2006 tivity of paracetamol. Thus, paracetamol acts as a pro-drug, the active one being a cannabinoid. These findings finally explain the mechanism of action of paracetamol and the peculiarity of its effects, including the behavioral ones. Curiously, just when the first CB 1 agonists are being introduced for pain treatment, it comes out that an indirect cannabinomimetic had been extensively used (and sometimes overused) for more than a century.

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“…These authors suggest that saturation of presystemic biotransformation occurs at doses greater than 500 mg, since the apparent bioavailability was significantly less after 500 mg and 650 mg than after 1000 mg or 2000 mg orally. On the other hand, Borin (6) reported that dose-corrected AVC at 1500 mg and 2000 mg of acetaminophen were significantly higher than 325 mg or 500 mg doses.…”

Section: Introductionmentioning

confidence: 99%

Acetaminophen presystemic biotransformation vs bioavailability in therapeutical dosage range

Goicoechea

Vila-Jato

1998

European Journal of Drug Metabolism and Pharmacokinetics

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The influence of dose on the absorption and presystemic biotransformation of acetaminophen was studied in 15 healthy volunteers after administration of 3 different oral doses (250 mg, 500 mg, 750 mg) following a 3 x 3 Latin Square Design. The analytical method developed (High Performance Liquid Chromatography, HPLC) allows the rapid and simultaneous determination of acetaminophen and its major metabolites (its glucuronide and sulphate conjugates) by direct injection of urine samples. The statistical analysis did not reveal significant differences (alpha < 0.05) among treatments in the percentage of dose excreted and MRT and VRT values. Consequently, our results indicate that the absorption and biotransformation of acetaminophen is not affected by the dose in the usual therapeutical range.

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Single dose bioavailability of acetaminophen following oral administration

Cited by 26 publications

References 18 publications

Semimechanistic model describing gastric emptying and glucose absorption in healthy subjects and patients with type 2 diabetes

Semimechanistic model describing gastric emptying and glucose absorption in healthy subjects and patients with type 2 diabetes

Paracetamol: New Vistas of an Old Drug

Acetaminophen presystemic biotransformation vs bioavailability in therapeutical dosage range

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