May 12, 2003: What is the bioavailability of rectally administered acetaminophen (Tylenol)?

Acetaminophen (APAP) is frequently administered as a rectal suppository.  The clinical assumption is that the absorption is good and that therapeutic concentrations are rapidly achieved.  This is not the case.  The evidence is as follows.
If 24 mg/kg of acetaminophen is administered to infants, serum drug concentrations are below the therapeutic range (10-20 mg/L)  (1) This data was corroborated in another report.  (2) Bioavailability of rectal APAP is about 78%.  (3) Although these studies had small numbers, results were consistent.  A study of 10 healthy adults confirmed.  35-45 mg/kg of APAP rectally is needed to achieve sustained therapeutic drug concentrations.  (4) 
Absorption is affected by the size of the suppository, rectal vault contents, pH, and colonic blood flow.  Not all suppositories are made equal.  Those with lipophilic bases have faster absorption rates than those with hydrophilic bases.  Interindividual variability is also a factor.  The authors from the above studies recommend approximately 40 mg/kg rectally to achieve therapeutic serum APAP concentration, which is accepted as the concentration required for antipyretic activity. 
Thanks to Marty Baker Pharm D. for research on this question of the week.
1.    Hansen TG, O’Brien K, Morton NS, Rasmussen SN.  Plasma paracetamol concentrations and pharmacokinetics following rectal administration in neonates and young infants.  Acta Anaesthesiol Scand 1999; 43:855-59. 
2.    Birmingham PK, Tobin MJ, Henthorn TK, Fisher DM, Berkelhamer MC, Smith FA, Fanta KB, Cote CJ.  Twenty-four-hour pharmacokinetics of rectal acetaminophen in children: an old drug with new recommendations.  Anesthesiology 1997; 87(2): 244-252.
3.    Coulthard KP, Nielson HW, Schroder M, Covino A, Matthews NT, Murray RS, Van der Walt JH.  Relative bioavailability and plasma paracetamol profiles of Panadol® suppositories in children.  J Paediatri Child Health 1998;34(5):424-31.
4.    Stocker ME, Montgomery JE.  Serum paracetamol concentrations in adult volunteers following rectal administration.  Br J Anest 2001; 87(4): 638-640.
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Donna Seger, M.D.
Medical Director, Middle Tennessee Poison Center