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Rectal paracetamol dosing regimens: determination by computer simulation
Author(s) -
ANDERSON B.J.,
HOLFORD N.H.G.
Publication year - 1997
Publication title -
pediatric anesthesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.704
H-Index - 82
eISSN - 1460-9592
pISSN - 1155-5645
DOI - 10.1046/j.1460-9592.1997.d01-125.x
Subject(s) - dosing , medicine , pharmacokinetics , plasma concentration , analgesic , anesthesia , acetaminophen , tonsillectomy , toxicity , loading dose , zoology , pharmacology , biology
A pharmacokinetic dynamic simulation model was used to predict rectal paracetamol dosing schedules which would maintain steady state plasma concentrations of 10–20 mg·l −1 . These plasma concentrations of paracetamol are known to reduce fever. The conventional dosing schedule of 15 mg·kg −1 four hourly was unsatisfactory. Steady state concentrations of 8–12 mg·l −1 were only reached after 16 h. A loading dose of 50 mg·kg −1 followed by 30 mg·kg −1 six hourly achieved plasma concentrations of 9–18 mg·l −1 . Paracetamol is a mild analgesic. A higher plasma paracetamol concentration of 25 mg·l −1 is known to give satisfactory analgesia to 60% of children after tonsillectomy. This concentration can be reached after a loading dose of 70 mg·kg −1 and a maintenance dose of 50 mg·kg −1 8 hourly. Doses above 150 mg·kg −1 ·day −1 have been reported to cause reversible liver toxicity after 2–8 days and should not be sustained.