The pharmacokinetics of a single rectal dose of paracetamol (40 mg·kg−1) in children with liver disease

Summary Background: The aim of our study was to measure the serum paracetamol concentrations achieved following a single rectal loading dose of 40 mg·kg−1 in children with chronic liver disease. Methods: We recruited 17 children (3–15 years, 10.6–75 kg) undergoing minor surgical procedures under general anesthesia. Paracetamol was administered at the end of surgery and blood samples were taken for analysis at 2, 3, 4, 6 and 8 h postdose. Results: The mean Cmax of 11.4 mg·l−1 [coefficient of variation (CV) 66%] was achieved at a Tmax of 2.7 h (CV 42%). The relative bioavailability (F) of the suppository formulation was not estimated, but clearance (Cl/F) estimates 0.73 l·kg−1·h−1 (CV 87%) and time–concentration profiles for these children were similar to the normal pediatric population. Conclusions: There are currently no biologic markers available for monitoring possible hepatotoxicity in this cohort of patients with liver disease, but our data suggest that a single‐dose suppository is a satisfactory analgesic alternative.