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

Objective. To determine whether multiple dosing of acetaminophen would resu lt in drug accumulation in polymedicated elderly patients with rheumatic pa in. Methods. Twelve inpatients (11 women), aged 89 +/- 4 years, weight 59 +/- 1 0 kg, receiving 3 to 8 concomitant medications, entered the study. Their cr eatinine clearance according to the Cockroft-Gault formula was 42 +/- 12 ml /min. The pharmacokinetics of 1 g acetaminophen was evaluated after the fir st dose (Dl)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 DI. No significant within-patient differen ces were observed, especially with respect to plasma elimination half-Life (2.74 +/- 0.48 and 2.77 +/- 0.32 hours, respectively), area under the conce ntration-time curve (82.5 +/- 21.1 and 90.1 +/- 15.2 mug.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 aceta minophen in these very rid subjects. On the basis of pharmacokinetic data a lone, a dose regimen of acetaminophen 1 g tid seems to be appropriate in su ch patients.