Kinetics of the Metabolism of Acetaminophen by Humans

Nelson, Eino; Morioka, Tadashi

doi:10.1002/jps.2600520911

Cited by 39 publications

(17 citation statements)

References 2 publications

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“…In the present investigation it was not possible to demonstrate differences in the absorption, excretion, or metabolism of phenacetin or APAP in subjects showing a marked renal tubular cell response com- 14 The mean urinary recovery as total APAP following treatment with phenacetin was lower than when AP AP was taken. This may have been due either to incomplete absorption of phenacetin or to the formation of metabolites which were not measured as p-aminophenol after hydrolysis of the urine with acid.…”

Section: Discussioncontrasting

confidence: 52%

The comparative metabolism of phenacetin and N‐acetyl‐p‐aminophenol in man, with particular reference to effects on the kidney

Prescott

Sansur

Levin

et al. 1968

Clin Pharma and Therapeutics

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Section: Discussioncontrasting

confidence: 52%

The comparative metabolism of phenacetin and N‐acetyl‐p‐aminophenol in man, with particular reference to effects on the kidney

Prescott

Sansur

Levin

et al. 1968

Clin Pharma and Therapeutics

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“…The kinetics of paracetamol absorption, distribution and elimination have been studied by many investigators (Nelson & Morioka, 1963;Cummings, King & Martin, 1967;Levy & Yamada, 1971;Prescott & Wright, 1973;0ie et al, 1975;Clements & Prescott, 1976;Briant et al, 1976;Rawlins, Henderson & Hijab, 1977;Clements, Heading, Nimmo & Prescott, 1978;and others). A new pharmacokinetic model has recently been developed to take into account the critical effect of variation in gastric emptying rate on paracetamol absorption in man.…”

Section: Kineticsmentioning

confidence: 99%

Kinetics and metabolism of paracetamol and phenacetin.

Prescott¹

1980

Brit J Clinical Pharma

396

279

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1 The rate of absorption of oral paracetamol depends on the rate of gastric emptying and is usually rapid and complete. The mean systemic availability is about 757o. 2 Paracetamol is extensively metabolized and the plasma half-life is 1.5-2.5 hours. About 55%o and 3007 of a therapeutic dose is excreted in the urine as glucuronide and sulphate conjugates, respectively, whereas mercapturic acid and cysteine conjugates (representing conversion to a potentially toxic intermediate metabolite) each account for some 4%o of the dose. Paracetamol metabolism is age-and dose-dependent. 3 With hepatotoxic doses, paracetamol metabolism is impaired and the half-life prolonged. Sulphate conjugation is saturated and the proportion excreted as mercapturic acid and cysteine conjugates is increased. 4 The renal clearance of paracetamol depends on urine flow rate by notpH. The renal clearances of' the glucuronide and sulphate conjugates often exceed the glomerular filtration rate and are independent of urine flow and pH. 5 Phenacetin absorption depends on formulation. It is extensively metabolized to paracetamol and minor metabolites are probably responsible for toxicity Paracetamol PARACETAMOL (acetaminophen, N-acetyl-p-aminophenol, 4-hydroxyacetanilide) is a moderately waterand lipid-soluble weak organic acid. It has a pKa value of 9.5 and is therefore largely unionized over the physiological range ofpH.

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“…Previously reported pharmacokinetic studies of paracetamol have been restricted to healthy subjects taking therapeutic doses under ideal conditions (Nelson & Morioka, 1963;Levy & Yamada, 1971). In the present study a detailed clinical pharmacokinetic analysis has been carried out in patients taking paracetamol in overdosage since abnormal drug metabolism and elimination is inevitable in the presence of acute hepatic or renal damage.…”

Section: Introductionmentioning

confidence: 99%

The effects of hepatic and renal damage on paracetamol metabolism and excretion following overdosage.: A pharmacokinetic study

Prescott¹,

Wright²

1973

British J Pharmacology

105

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Summary The kinetics of paracetamol metabolism and excretion were studied in 41 patients following overdosage. Acute hepatic necrosis developed in 23 patients and in 3 of these acute renal failure also occurred. Two patients died in hepatic failure. Paracetamol metabolism was impaired in the patients with liver damage. The plasma half‐life of the unchanged drug was significantly prolonged, and the ratio of the plasma concentrations of unchanged to conjugated paracetamol was significantly higher than in the patients without liver damage. Paracetamol and its conjugates were rapidly excreted in the urine. However, excretion was slower in patients with liver damage and a higher proportion was excreted unchanged. The renal clearance of unchanged (but not conjugated) paracetamol was related to the urine flow rate. However, forced diuresis is of no practical value and is contraindicated on clinical grounds. There was no correlation between urine pH and clearance of unchanged or conjugated drug. In patients with hepatic necrosis there was a marked decrease in the overall elimination rate constant which could be accounted for by decreased metabolite formation. Except in patients with acute renal failure, the urinary excretion rate constants were similar to those observed in patients without liver damage.

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Kinetics of the Metabolism of Acetaminophen by Humans

Cited by 39 publications

References 2 publications

The comparative metabolism of phenacetin and N‐acetyl‐p‐aminophenol in man, with particular reference to effects on the kidney

The comparative metabolism of phenacetin and N‐acetyl‐p‐aminophenol in man, with particular reference to effects on the kidney

Kinetics and metabolism of paracetamol and phenacetin.

The effects of hepatic and renal damage on paracetamol metabolism and excretion following overdosage.: A pharmacokinetic study

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