Pharmacokinetic comparison of acetaminophen elixir versus suppositories in vaccinated infants (aged 3 to 36 months): a single-dose, open-label, randomized, parallel-group design.
BACKGROUND
Because of practical problems and ethical concerns, few studies of the pharmacokinetics (PK) of acetaminophen (ACET) in infants have been published.


OBJECTIVE
The goal of this study was to compare the PK of an ACET rectal suppository with a commercially available ACET elixir to complete a regulatory obligation to market the suppository. This study was not submitted previously because of numerous obstacles related to both the investigators and the commercial entities associated with the tested product.


METHODS
Thirty infants (age 3-36 months) prescribed ACET for either fever, pain, or postimmunization prophylaxis of fever and discomfort were randomized to receive a single 10- to 15-mg/kg ACET dose either as the rectal suppository or oral elixir. Blood was collected at selected times for up to 8 hours after administration. ACET concentrations were measured by using a validated HPLC method, and PK behavior and bioavailability were compared for the 2 preparations.


RESULTS
All 30 infants enrolled were prescribed ACET for postimmunization prophylaxis. PK samples were available in 27 of the 30 enrolled infants. Subject enrollment (completed in January 1995) was rapid (8.3 months) and drawn entirely from a vaccinated infant clinic population. There were no statistically significant differences between the subjects (elixir, n = 12; suppository, n = 15) in either mean (SD) age (10.0 [6.3] vs 12.4 [8.1] months), weight (8.6 [2.3] vs 9.4 [2.4] kg), sex (7 of 12 males vs 7 of 15 males), or racial distribution (5 white, 5 black, and 2 biracial vs 4 white and 11 black) between the 2 dosing groups (oral vs rectal, respectively). The oral and rectal preparations produced similar, rapid peak concentrations (T(max), 1.16 vs 1.17 hours; P = 0.98) and elimination t(½) (1.84 vs 2.10 hours; P = 0.14), respectively. No statistically significant differences were found between either C(max) (7.65 vs 5.68 μg/mL) or total drug exposure (AUC(0-∞), 23.36 vs 20.45 μg-h/mL) for the oral versus rectal preparations. There were no serious treatment-related effects noted. Delays in submitting this work for publication were the result of a number of investigator and sponsor issues despite the study's positive outcome.


CONCLUSIONS
No statistically significant differences were found between the rates or extent of absorption of the suppository and elixir preparations in this small, infant population. Both preparations were well tolerated. Vaccinated infants were a useful population in which to conduct a PK study of this antipyretic, analgesic product. Delays in publishing pediatric trials can occur as a result of a number of issues even when results are positive.
Department of Clinical Pharmacology and Toxicology, Columbus Children's Hospital, Columbus, OH, USA. pwalson1@aol.com
Philip D
PD
Walson
Mark
M
Halvorsen
James
J
Edge
Marcel J
MJ
Casavant
Michael T
MT
Kelley
D000082:Acetaminophen / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002675:Child, Preschool; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D008297:Male; D008657:Metabolic Clearance Rate; D044469:Racial Groups; D012996:Solutions; D013488:Suppositories
D018712:Analgesics, Non-Narcotic; D012996:Solutions; D013488:Suppositories; D000082:Acetaminophen