Clinical Pharmacokinetics of Paracetamol

  title={Clinical Pharmacokinetics of Paracetamol},
  author={John A. H. Forrest and Judith A. Clements and Laurie F. Prescott},
  journal={Clinical Pharmacokinetics},
SummaryIn therapeutic doses paracetamol is a safe analgesic, but in overdosage it can cause severe hepatic necrosis. Following oral administration it is rapidly absorbed from the gastrointestinal tract, its systemic bioavailability being dose-dependent and ranging from 70 to 90%. Its rate of oral absorption is predominantly dependent on the rate of gastric emptying, being delayed by food, propantheline, pethidine and diamorphine and enhanced by metoclopramide. Paracetamol is also well absorbed… 

Acetaminophen (Paracetamol) Oral Absorption and Clinical Influences

An understanding of the sites and features of acetaminophen absorption—and how they might be influenced by factors encountered in clinical practice—is important for pain management using this agent.

Acetaminophen: a practical pharmacologic overview.

Acetaminophen poisoning follows an acute overdose and is manifested clinically by an initial phase of nonspecific signs and symptoms, a latent period in which the liver transaminase levels rise and then, 3 to 5 days after the ingestion, signs of more serious hepatic dysfunction.

The Pharmacokinetic Profile of Intravenous Paracetamol in Adult Patients Undergoing Major Abdominal Surgery

After major abdominal surgery, there were apparent increases in the metabolic conversion to paracetamol glucuronide and its urinary clearance suggesting potential induction of par acetaml glucuronidation.

Analgesic activity of a thiomethyl metabolite of paracetamol

This work has compared the analgesic effect of paracetamol and 3MT-4HA after oral administration to mice under strictly identical conditions.

Paracetamol disposition and metabolite kinetics in patients with chronic renal failure

In the patients with moderate renal failure the AUC's of the glucuronide and sulphate conjugates were related to the plasma creatinine and there were significant negative correlations with the renal clearances of these metabolites and total urinary recovery.

Paracetamol metabolism in patients with ulcerative colitis.

Results do not indicate a general impairment of the systemic capacity for sulphation of paracetamol in patients with ulcerative colitis, and metabolic clearances to the sulphate, glucuronide and glutathione derived metabolites were not significantly different.

Pharmacokinetic properties of intramuscular versus oral syrup paracetamol in Plasmodium falciparum malaria

Paracetamol plasma concentrations after oral syrup and intramuscular administration in patients with acute falciparum malaria were described successfully by a two-compartment disposition model, with zero-order and first-order absorption for intamuscular and oral syrup administration, respectively.

The disposition of paracetamol and the accumulation of its glucuronide and sulphate conjugates during multiple dosing in patients with chronic renal failure

Predictions of steady-state concentrations based on previous studies with single doses of paracetamol in renal failure patients were remarkably accurate for the glucuronide but not for the sulphate conjugate, consistent with some extra-renal elimination of retained par acetamol conjugates in patients with chronic renal failure, with limited regeneration of the parent compound.

Paracetamol and Phenacetin

The pre-eminent position of paracetamol and aspirin as the non-narcotic analgesic agents of choice for mild to moderate pain is being seriously challenged by ‘newer’ non-steroidal anti-inflammatory drugs.

Pharmacokinetics of Paracetamol in Göttingen Minipigs: In Vivo Studies and Modeling to Elucidate Physiological Determinants of Absorption

Gastric transit times in overnight fasted minipigs are longer than those observed in humans and this is most likely caused by delayed and incomplete food emptying and further work is needed to develop feasible and effective fasting protocols for minIPigs.



Kinetics and metabolism of paracetamol and phenacetin.

  • L. Prescott
  • Medicine, Biology
    British journal of clinical pharmacology
  • 1980
It is found that Phenacetin absorption depends on formulation, and it is extensively metabolized to paracetamol and minor metabolites are probably responsible for toxicity.


The AUCpO /AUCLv ratio cannot be used as a measure of bioavailability if clearance after oral administration is different from clearance after intravenous administration, and simultaneous measurements of drug levels in both plasma and urine may be essential when studying the bioavailability of drugs.

Paracetamol (acetaminophen) clearance in patients with cirrhosis of the liver.

Steady-state levels of paracetamol were significantly increased in the patients with cirrhosis of the liver and a significant correlation between the values of plasma clearance of par acetamol and prothrombin time and galactose elimination capacity was found.

Effects of microsomal enzyme induction on paracetamol metabolism in man.

Conversion of paracetamol to its potentially hepatotoxic metabolite does not seem to be increased in patients induced with anticonvulsants or rifampicin, and there would seems to be no contraindication to the use of these drugs in combination.

Antipyrine, paracetamol, and lignocaine elimination in chronic liver disease.

The plasma half lives of antipyrine, paracetamol, and lignocaine given by mouth were measured in patients with stable chronic liver diseases of varying severity to suggest that impaired drug elimination was related to depressed hepatic protein synthesis.

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

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 and forced diuresis is of no practical value and is contraindicated on clinical grounds.

Paracetamol overdose in man: relationship between pattern of urinary metabolites and severity of liver damage.

Higher quantities of paracetamol conjugates were recovered from patients who developed moderate of severe liver damage than those less severely affected, although correlations in individuals between quantity excreted and clinical outcome was poor.

The gastrointestinal absorption of paracetamol in the rat

The absorption of [3H]paracetamol by rat small intestine, colon and stomach was studied in vivo and in vitro, suggesting that the uptake of paracetaml is by a passive transport process and confirming the efficiency of par acetamol absorption observed indirectly by others.

Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs.

It is suggested that the lower bioavailability of paracetamol in the epileptic patients results from enhancement of first-pass metabolism, secondary to enzyme induction.

Paracetamol metabolism following overdosage: application of high performance liquid chromatography

The pattern of urinary excretion of paracetamol metabolites did not appear to be influenced by the treatment given, but was related to the severity of liver damage (Table 1), which was significantly less in Patients with severe liver damage than in those without.