OBJECTIVE: To compare the pharmacokinetics of Tylenol Extended Relief (ER APAP) with those of immediate-release acetaminophen (IR APAP) at supratherapeutic doses. METHODS: A prospective, double-blind, randomized, crossover comparison trial involving 14 adult volunteers. Each subject ingested 75 mg/kg of either ER APAP or IR APAP and 1 week later received the other APAP preparation. On both occasions plasma APAP concentration ([APAP]) was determined 0.5, 1, 2, 3, 4, 6, 8, 12, and 16 hours after ingestion. The times to maximum [APAP] (Tmax); the maximum [APAP] values (Cmax); the elimination half-lives 4-16 hours postingestion (t1/2), and the areas under the [APAP] vs time curve (AUC) for ER APAP and IR APAP were compared using the paired t-test. RESULTS: All the subjects completed both study phases. The mean APAP dose ingested was 5.6 g (range 4.2-7.8 g). Both the AUC and the Cmax were less after ER APAP than after IR APAP; otherwise, there was no evident difference in any measure. Graphically, ER APAP yielded a flatter, plateau-shaped curve initially, but after 4 hours the curve was nearly identical to that for IR APAP. Results are summarized in the table: [table: see text] CONCLUSION: In this model involving a single supratherapeutic dose, ER APAP evidenced no pharmacokinetic features that would suggest the need for an alternate poisoning screening strategy. When compared with IR APAP, ER APAP had a lower AUC, all peak [APAP] occurred in < 4 hours, and terminal eliminations were identical. The data suggest that, in most cases, the diagnostic approach to an overdose of ER APAP need not deviate from that used for an IR APAP overdose.
RCT Entities:
OBJECTIVE: To compare the pharmacokinetics of Tylenol Extended Relief (ER APAP) with those of immediate-release acetaminophen (IR APAP) at supratherapeutic doses. METHODS: A prospective, double-blind, randomized, crossover comparison trial involving 14 adult volunteers. Each subject ingested 75 mg/kg of either ER APAP or IR APAP and 1 week later received the other APAP preparation. On both occasions plasma APAP concentration ([APAP]) was determined 0.5, 1, 2, 3, 4, 6, 8, 12, and 16 hours after ingestion. The times to maximum [APAP] (Tmax); the maximum [APAP] values (Cmax); the elimination half-lives 4-16 hours postingestion (t1/2), and the areas under the [APAP] vs time curve (AUC) for ER APAP and IR APAP were compared using the paired t-test. RESULTS: All the subjects completed both study phases. The mean APAP dose ingested was 5.6 g (range 4.2-7.8 g). Both the AUC and the Cmax were less after ER APAP than after IR APAP; otherwise, there was no evident difference in any measure. Graphically, ER APAP yielded a flatter, plateau-shaped curve initially, but after 4 hours the curve was nearly identical to that for IR APAP. Results are summarized in the table: [table: see text] CONCLUSION: In this model involving a single supratherapeutic dose, ER APAP evidenced no pharmacokinetic features that would suggest the need for an alternate poisoning screening strategy. When compared with IR APAP, ER APAP had a lower AUC, all peak [APAP] occurred in < 4 hours, and terminal eliminations were identical. The data suggest that, in most cases, the diagnostic approach to an overdose of ER APAP need not deviate from that used for an IR APAPoverdose.
Authors: Marlon J A Jetten; Ainhoa Ruiz-Aracama; Maarten L J Coonen; Sandra M Claessen; Marcel H M van Herwijnen; Arjen Lommen; Joost H M van Delft; Ad A C M Peijnenburg; Jos C S Kleinjans Journal: Arch Toxicol Date: 2015-06-24 Impact factor: 5.153
Authors: Juan G Diaz Ochoa; Joachim Bucher; Alexandre R R Péry; José M Zaldivar Comenges; Jens Niklas; Klaus Mauch Journal: Front Pharmacol Date: 2013-01-22 Impact factor: 5.810