Absolute and relative bioavailability of oral acetaminophen preparations

Eighteen healthy volunteers received single 650-mg doses of acetaminophen by 5-min intravenous infusion, in tablet form by mouth in the fasting state, and in elixir form orally in the fasting state in a three-way crossover study. An additional eight subjects received two 325-mg tablets from two commercial vendors in a randomized crossover fashion. Concentrations of acetaminophen in multiple plasma samples collected during the 12-hr period after each dose were determined by high-performance liquid chromatography. Following a lag time averaging 3-4 min, absorption of oral acetaminophen was first order, with apparent absorption half-life values averaging 8.4 (elixir) and 11.4 (tablet) min. The mean time-to-peak concentration was significantly longer after tablet (0.75 hr) than after elixir (0.48 hr) administration. Peak plasma concentrations and elimination half-lives were similar following both preparations. Absolute systemic availability of the elixir (87%) was significantly greater than for the tablets (79%). Two commercially available tablet formulations did not differ significantly in peak plasma concentrations, time-to-peak, or total area under the plasma concentration curve and therefore were judged to be bioequivalent.