Pharmacokinetics of paracetamol vary in frail octogenarians

The pharmacokinetics parameters of oral paracetamol show wide differences among hospitalized octogenarians following multiple dosing, with female sex and higher total serum bilirubin concentrations correlating with drug exposure, a recent study has shown. In addition, there are no significant differences between the tablet and granulate formulations.

Geriatric inpatients (mean age 86.78 years) received a 1,000-mg paracetamol tablet or granulate at 08:00, 14:00, and 20:00. Plasma samples were obtained around the 08:00 dose (trough, +0.5, +1, +2, +4, +5, and +6 h) after at least four consecutive gifts.

The authors determined plasma concentrations of paracetamol and its metabolites and derived individual pharmacokinetic parameters. They also assessed frailty using the Edmonton Frail Scale. An analgesic plasma target was defined as an average plasma concentration (C_avg) of 10 mg/L.

Thirty-six hospitalized patients were included, of whom 26 (72 percent) received the tablet and 10 (28 percent) the granulate. Thirty patients (85 percent) were classified as having moderate-to-severe frailty, and seven (21 percent) had a C_avg >10 mg/L.

The median time to reach the peak concentration was 50.5 min (interquartile range [IQR], 31.50‒92.50) for the tablet and 42.50 min (IQR, 33.75‒106.75) for the granulate. The coefficient of variation was 95 percent for time to reach the peak concentration and 30 percent for C_avg of paracetamol.

Notably, the C_avg of paracetamol was associated with female sex and total serum bilirubin.