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 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).


CONCLUSIONS
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.
Bannwarth
B
B
Department of Rheumatology, Groupe Hospitalier Pellegrin, Bordeaux, France. bernard.bannwarth@thera.u-bordeaux2.fr
Pehourcq
F
F
Lagrange
F
F
Matoga
M
M
Maury
S
S
Palisson
M
M
Le Bars
M
M
D000082:Acetaminophen / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D004359:Drug Therapy, Combination; D005260:Female; D016330:Frail Elderly; D006801:Humans; D008297:Male; D010146:Pain / Q000188:drug therapy*; D012216:Rheumatic Diseases / Q000188:drug therapy / Q000378:metabolism*
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen