Plasma acetaminophen concentration

Fig. 5 Plasma acetaminophen concentration following the oral administration of acetaminophen and its ethyl vinyl ether prodrug. Dog 1 received lOmg/kg doses of acetaminophen (O) and the prodrug ( ). Dog 2 received 25mg/kg doses of acetaminophen ( ) and the prodrug ( ). The 0.5-h prodrug and 8-h acetaminophen samples for dog 2 could not be obtained. (From Ref. " f)...

Fig. 13. Dose-related effects of EM574 top), motilin middle), and cisapride bottom) on gastric antral motor index left) and gastric emptying indicated as plasma acetaminophen concentration right). EM574 and cisapride were administered intraduodenally immediately after the meal. Motilin was infused intravenously during 30-min postprandial period. Data are expressed as means SE of five dogs. E < 0.05, E < 0.01 compared to each control by paired t test with Bonferroni s correction. (From Sato et al. [22] with permission from Elsevier Science.)...

Levy G, Khanna NN, Soda DM, Tsuzuki O, Stern L (1975) Pharmacokinetics of acetaminophen in the human neonate Formation of acetaminophen glucuronide and sulphate in relation to plasma bilirubin concentration and d-glucaric acid excretion. Pediatrics, 55 818-825. 

Levin GM, Gram C, Eisele G. Effect of over-the-counter dosages of naproxen sodium and acetaminophen on plasma lithium concentrations in normal volunteers. J Clin Psychopharmacol 1998 18(3) 237 10. 

When plasma concentrations are below the nomogram treatment line, there is little risk of toxicity, protective therapy with acetylcysteine is not necessary, and further medical therapy is unnecessary for the acetaminophen overdose. The acetaminophen blood sample should be drawn no sooner than 4 hours after the ingestion to ensure that peak acetaminophen concentrations have been reached. 

Fig. 14 (A, B) Maximum acetaminophen plasma concentration (Cmax) and time to achieve that concentration (TmllK) as a function of gastric emptying half-time. (From Ref. 82.) (C) Percent of an acetaminophen dose emptied from the stomach (O) and acetaminophen plasma concentrations ( ) as a function of time in one subject. (D) The same plot and for the same subject as in (C) after a 10 mg intramuscular dose of heroin. (C and D from Ref. 83.)...

All the above mentioned polymers have been evaluated mainly for application in the intestine. Finally, the last part of the gastrointestinal tract, the rectum should also be mentioned as a suitable site for delivery and fast absorption of therapeutics. Kim et al. [88] developed an in situ gelling and mucoadhesive acetaminophen liquid suppository prepared with poloxamers and sodium alginate. It was found that this particular formulation of acetaminophen in humans resulted in shorter T ax and higher maximum plasma concentrations of dmg (C ax) than the conventional acetaminophen suppositories. 

Paracetamol, synonym acetaminophen, is world wide probably the most popular analgesic and antipyretic. Its mechanism of action is not well understood. It is not really an NSAID as it is only a very weak inhibitor of cyclo-oxygenase and has hardly any anti-inflammatory activity. For the same reason paracetamol gives only negligible gastrointestinal irritation and gives hardly any blockade of platelet aggregation. Paracetamol concentrations in plasma reach a peak in 30-60 minutes, and the half-life in plasma is about 2 hours. Almost 100% of... 

Some work has demonstrated that pulse voltammetry at the carbon paste electrode can be applied to the assay of drugs in body fluids [197,198]. Methods based on the electrooxidation of theophylline [197] and acetaminophen [198] were described at concentrations of approximately 5-10 fxg/mL plasma. 

In adults, hepatotoxicity may occur after ingestion of a single dose of acetaminophen (10-15 g) doses of 20-25 g or more are potentially fatal. Severe liver damage occurs in 90 percent of patients with plasma concentrations of acetaminophen in excess of 300 pg/ml at 4 hours or 45 pg/rnl at 15 hours after ingestion of the drug. Administration of N-acetylcysteine is recommended if less than 36 hours has elapsed since ingestion of acetaminophen, although the antidote is most effective if administered within 10 hours. 

An HPLC method for the more difficult measurement of plasma free metanephrines was first described in 1993. This method, like those involving measurements of plasma or urinary deconjugated metanephrines, requires a preana-lytical cation-exchange extraction and purification step. The low plasma concentrations of free metanephrines present several technical challenges. In particular, low levels of interfering substances, such as acetaminophen, tend to be more troublesome to measurements of plasma concentrations of the free metabolites than to the higher decon-... 

More complicated isobolograms exist. The N-acetyl cysteamine dosage algorithm is an isobologram with time and acetaminophen (paracetamol) plasma concentration on the axes in the plane of the paper and a two-step measure in the third dimension (probability of toxicity that requires treatment). Somewhat as famous is Professor Herxheimer s depiction of the interaction between coffee and wine two glasses of each provide the maximum possible beneficial effect (the effect being happiness ). The contours are thus of a hill on a plane. 

The toxicity of acetaminophen/paracetamol is plasma concentration dependent. However, it should be remembered that plasma concentra-... 

If the plasma concentration plotted on the nomogram falls above the nomogram treatment line, indicating that hepatic damage is possible, a full course of treatment with acetylcysteine is indicated. When the results of the acetaminophen determination will be available later than 8 hours after the ingestion, acetylcysteine therapy should be... 

Although young children have an inherently lower risk of acetaminophen-induced hepatotoxicity, these patients should be managed in the same manner as adults. When acetaminophen plasma concentrations predict that toxicity is probable, young children should receive acetylcysteine in the dosing regimen described previously. ... 

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