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Pharmacokinetic Effects of Diphenhydramine or Oxycodone in Simulated Acetaminophen Overdose
Author(s) -
Halcomb S. Eliza,
Sivilotti Marco L.A.,
Goklaney Anil,
Mullins Michael E.
Publication year - 2005
Publication title -
academic emergency medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.221
H-Index - 124
eISSN - 1553-2712
pISSN - 1069-6563
DOI - 10.1111/j.1553-2712.2005.tb00859.x
Subject(s) - acetaminophen , medicine , diphenhydramine , pharmacokinetics , cmax , oxycodone , anesthesia , pharmacology , crossover study , absorption (acoustics) , area under the curve , opioid , receptor , histamine , physics , alternative medicine , pathology , acoustics , placebo
Objectives: To determine the effects of co‐ingested diphenhydramine (DPH) or oxycodone (OXY) on the absorption kinetics of simulated acetaminophen (APAP) overdose. Methods: This was an institutional review board–approved, prospective crossover study of ten healthy human volunteers ingesting 5 grams of APAP, 5 grams of APAP + 250 mg of DPH (APAP+DPH), or 5 grams of APAP + 0.5 mg/kg of OXY (APAP+OXY). Serum APAP concentrations (APAPs) were measured hourly from zero through eight hours and again at 24 hours, and basic noncompartmental pharmacokinetic parameters were compared. Results: For APAP alone, the mean parameters were: maximum APAP concentration ([APAP] max ) 71.8 μ g/mL, time to peak [APAP] (t max ) 1.71 hours, and area under the receiver operating characteristic curve (AUC 0–8 ) 318.3 μ g‐hr/mL. For APAP+DPH, the mean parameters were: [APAP] max 67.6 μ g/mL, t max 1.90 hours, and AUC 0–8 297.7 μ g‐hr/mL. For APAP+OXY, the parameters were: [APAP] max 42.9 μ g/mL, t max 2.87 hours, and AUC 0–8 232.1 μ g‐hr/mL. Compared with APAP alone, APAP+OXY had a 27% lower AUC, a 40% lower [APAP] max , and a 68% longer t max . Co‐ingested DPH had no significant effect on APAP absorption, except a 6% decrease in the AUC. Conclusions: Co‐ingested OXY, but not DPH, delayed absorption of APAP. This suggests a potential role for activated charcoal administration beyond one hour postingestion after mixed ingestions that include OXY.