Single and multiple dose pharmacokinetics of acetaminophen (paracetamol) in polymedicated very old patients with rheumatic pain

Abstract

Objective: To determine whether multiple dosing of acetaminophen would result in drug accumulation in polymedicated elderly patients with rheumatic pain.

Methods: Twelve inpatients (11 women), aged 89 +/- 4 years, weight 59 +/- 10 kg, receiving 3 to 8 concomitant medications, entered the study. Their creatinine clearance according to the Cockroft-Gault formula was 42 +/- 12 ml/min. The pharmacokinetics of 1 g acetaminophen was evaluated after the first dose (D1) and after the last dose (D7) during a 3 times daily regimen of 1 g for 5 consecutive days.

Results: The plasma pharmacokinetic profile of acetaminophen did not change significantly at D7 compared to D1. No significant within-patient differences were observed, especially with respect to plasma elimination half-life (2.74 +/- 0.48 and 2.77 +/- 0.32 hours, respectively), area under the concentration-time curve (82.5 +/- 21.1 and 90.1 +/- 15.2 microg x h/ml, respectively), and apparent oral clearance (3.68 +/- 0.85 and 3.28 +/- 0.52 ml/min/kg, respectively).

Conclusion: No drug accumulation occurred during multiple dosing with acetaminophen in these very old subjects. On the basis of pharmacokinetic data alone, a dose regimen of acetaminophen 1 g tid seems to be appropriate in such patients.