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 ofAPAP + 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 microg/mL, time to peak [APAP] (t(max)) 1.71 hours, and area under the receiver operating characteristic curve (AUC(0-8)) 318.3 microg-hr/mL. For APAP+DPH, the mean parameters were: [APAP](max) 67.6 microg/mL, t(max) 1.90 hours, and AUC(0-8) 297.7 microg-hr/mL. For APAP+OXY, the parameters were: [APAP](max) 42.9 microg/mL, t(max) 2.87 hours, and AUC(0-8) 232.1 microg-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.
RCT Entities:
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 microg/mL, time to peak [APAP] (t(max)) 1.71 hours, and area under the receiver operating characteristic curve (AUC(0-8)) 318.3 microg-hr/mL. For APAP+DPH, the mean parameters were: [APAP](max) 67.6 microg/mL, t(max) 1.90 hours, and AUC(0-8) 297.7 microg-hr/mL. For APAP+OXY, the parameters were: [APAP](max) 42.9 microg/mL, t(max) 2.87 hours, and AUC(0-8) 232.1 microg-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.
Authors: Marina Serper; Michael S Wolf; Nikhil A Parikh; Holly Tillman; William M Lee; Daniel R Ganger Journal: J Clin Gastroenterol Date: 2016-01 Impact factor: 3.062
Authors: L P James; E V Capparelli; P M Simpson; L Letzig; D Roberts; J A Hinson; G L Kearns; J L Blumer; J E Sullivan Journal: Clin Pharmacol Ther Date: 2008-10-15 Impact factor: 6.875