Pharmacokinetics of Intravenous Paracetamol in Elderly Patients

Intravenous paracetamol (N-acetyl-paraminophenol, acetaminophen) is a widely used nonopioid analgesic which has become popular in the treatment of pain in many patient groups, including the elderly. Although intravenous paracetamol has been studied widely in clinical analgesia studies, there is little information on its pharmacokinetics in the elderly. We designed this study to determine the pharmacokinetics of intravenous paracetamol in very old patients and to compare them with that of younger patients. We also considered the effect of adenosine triphosphate-binding cassette G2 protein (ABCG2) genotype and renal function on paracetamol pharmacokinetics in these patients.

In the group aged 80–90 years, the mean value of the area under the plasma concentration-time curve extrapolated to infinity (AUC_∞) of paracetamol was 54–68% higher than in the two youngest groups. Paracetamol clearance showed a statistically significant dependence on age group, whereas volume of distribution during elimination and elimination half-life were associated with age group and sex, respectively. Based on mean AUC_∞ of paracetamol glucuronide and paracetamol sulphate, the oldest patients had 1.3- to 1.5-fold greater exposure to these metabolites than patients aged 20–40 years. ABCG2 genotype did not affect paracetamol pharmacokinetics. There was a linear correlation between the values of AUC_∞ of paracetamol, its glucuronide and sulphate metabolites and GFR.

Trial registration number (EudraCT): 2006-001917-14