BACKGROUND: The aim of our study was to measure the serum paracetamol concentrations achieved following a single rectal loading dose of 40 mg x 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 x 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 x kg(-1) x 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.
BACKGROUND: The aim of our study was to measure the serum paracetamol concentrations achieved following a single rectal loading dose of 40 mg x 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 x 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 x kg(-1) x 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.
Authors: Mitchell R McGill; Laura P James; Sandra S McCullough; Jeffery H Moran; Samuel E Mathews; Eric C Peterson; Davis P Fleming; Morgan E Tripod; Joel H Vazquez; Stefanie Kennon-McGill; Horace J Spencer; Jonathan A Dranoff Journal: Hepatol Commun Date: 2021-08-25