The pharmacokinetics of a single rectal dose of paracetamol (40 mg x kg(-1)) in children with liver disease.
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.
Cormack
C R H
CR
Department of Anaesthetics, King's College Hospital, London, UK.
Sudan
S
S
Addison
R
R
Keating
J
J
Sherwood
R A
RA
Ashley
E M C
EM
Howell
Tanya
T
D000082:Acetaminophen / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000285:Administration, Rectal; D000293:Adolescent; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000768:Anesthesia, General; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008107:Liver Diseases / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen