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Relative bioavailability and plasma paracetamol profiles of Panadol ® suppositories in children
Author(s) -
COULTHARD KP,
NIELSON HW,
SCHRODER M.,
COVINO A,
MATTHEWS NT,
MURRAY RS,
VAN DER WALT JH
Publication year - 1998
Publication title -
journal of paediatrics and child health
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.631
H-Index - 76
eISSN - 1440-1754
pISSN - 1034-4810
DOI - 10.1046/j.1440-1754.1998.00267.x
Subject(s) - suppository , medicine , bioavailability , rectal administration , cmax , pharmacokinetics , antipyretic , absorption (acoustics) , oral administration , tonsillectomy , anesthesia , analgesic , pharmacology , physics , acoustics
Objective: To determine the relative bioavailability and plasma paracetamol concentration profiles following administration of a proprietary formulation of paracetamol suppositories to postoperative children. Methodology and Results: Study A—eight children undergoing minor surgery had blood samples collected following the rectal administration of either a 250 mg or 500 mg paracetamol suppository on one day and an equivalent oral dose on the following day. A mean dose of 13 mg/kg gave a mean Cmax (Tmax) of 7.7 mg/L (1.6 h) and 4.9 mg/L (2.0 h) following oral and rectal administration, respectively. The mean relative rectal bioavailability was 78% (95% confidence interval of 55–101%). Study B—20 children undergoing tonsillectomy and/or adenoidectomy were randomly assigned to receive a postoperative dose of 500 mg of paracetamol either as 2×250 mg liquid filled or 1×500 mg hard wax Panadol ® suppository. A mean dose of 25 mg/kg produced mean maximum plasma paracetamol concentrations of 13.2 mg/L and 14.5 mg/L at 2.1 and 1.9 h for the hard and liquid filled suppository, respectively. The absorption rate constants and areas under the curves suggested no difference in the rate or extent of absorption between the two formulations. Conclusion: Absorption of paracetamol following rectal administration of Panadol ® suppositories to postoperative children is slower and reduced as compared to oral therapy. The hard wax and liquid filled products have similar absorption characteristics. The usually quoted antipyretic therapeutic range for paracetamol is 10–20 mg/L, although 5 mg/L may be effective. A single rectal dose of 25 mg/kg will obtain this lower concentration within 1 h of administration and maintain it for up to 6 h. When given in an appropriate dose for analgesia, maximum plasma paracetamol concentrations would be available in the immediate postoperative period if the rectal dose was given 2 h before the planned end of the procedure.