Rectal paracetamol dosing regimens: determination by computer simulation.
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.
Anderson
B J
BJ
Department of Pharmacology and Clinical Pharmacology, Auckland University, New Zealand.
Holford
N H
NH
D000082:Acetaminophen / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D000285:Administration, Rectal; D000293:Adolescent; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D004334:Drug Administration Schedule; D005334:Fever / Q000188:drug therapy; D005544:Forecasting; D006801:Humans; D007223:Infant; D008099:Liver / Q000187:drug effects; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D008956:Models, Chemical; D010149:Postoperative Pain / Q000188:drug therapy; D013488:Suppositories; D014068:Tonsillectomy / Q000009:adverse effects
D018712:Analgesics, Non-Narcotic; D013488:Suppositories; D000082:Acetaminophen