Serum paracetamol concentrations in adult volunteers following rectal administration

Paracetamol is usually given in adults at a dose of 10-20 mg kg(-1) orally or rectally. Work in children suggests that doses of 40 mg kg(-1) are needed to provide therapeutic concentrations when this drug is used by the rectal route. We have investigated the dose of rectal paracetamol needed to achieve serum concentrations within the accepted therapeutic range of 10-20 mug ml(-1) in adults. Ten healthy adult volunteers received increasing doses of rectal paracetamol (15, 25, 35, and 45 mg kg(-1)). Following suppository administration, serum paracetamol concentrations were measured half hourly to 4 h then hourly to 8 h. Sustained concentrations within our therapeutic range were achieved with 35 and 45 mg kg(-1). Maximum measured concentrations were 12.5 (10-16), 16.5 (14-20), and 20 (17.5-23) mug ml(-1), median (Inter-quartile range) after 25, 35, and 45 mg kg(-1), respectively. We conclude that doses of 35-45 mg kg(-1) of rectal paracetamol are needed to achieve sustained therapeutic plasma concentrations in healthy adult volunteers.