Pharmacokinetics of paracetamol in adults after cardiac surgery

The phamacokinetics of paracetamol in adults after cardiac surgery have not been described Twenty patients were randomized to receive either paracetam ol 2 g through a nasogastric tube and as a suppository eight hours later or vice versa. Arterial blood samples were taken at 0.5, one, two, four, six and eight hours after dosing. Each patient was studied for 16 h. There were 16 males and thr-ee females. One patient was excluded because of sampling en ors. The mean age was 59 (SD 8) years and the mean weight 84 kg (16), The time-concentration profiles for each individual were used to estimate p harmacokinetic parameters using a non-linear mixed effects model (NONMEM). Population parameter estimates with coefficient of variation (CV%), standar dized to a 70 kg person, for a one-compartment model with first order input , lag time and first order, elimination were volume of distribution 127 l ( 28) and clearance 26.4 l/h (29) Rectal paracetamol had an absorption half-l ife (T-abs) of 2.02h (31) with a lag time of 0.28h, The absorption half-lif e for the oral preparation was 1.49h (81) with a lag time of 0.17h. The rel ative bioavailability of the rectal compared to the oral formulation was 0. 98 (18). Concentrations after either nasogastric or rectal paracetamol 2g were below a target concentration of 10 mg/l, which is associated with analgesia. Abs orption after nasogastric administration was slow compared to healthy adult s (T-abs 0.06 to 0.7h) and the bioavailability was half that expected, due to nasogastric loss. parameter estimates had large variability. Paracetamol is unlikely to have useful clinical impact in the majority of patients whe n standard doses (6 g/day) are given on day 1 after cardiac surgery.