Comparative pharmacokinetics of Panadol Extend and immediate-release paracetamol in a simulated overdose model

Cliff Tan, Andis Graudins

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18 Citations (Scopus)

Abstract

Background: Panadol Extend is a modified-release paracetamol formulation in which each 665 mg tablet contains 69 slow-release and 31 immediate-release paracetamol. There are no data on Panadol Extend pharmacokinetics in overdose. It is unknown whether the paracetamol treatment nomogram can be used to make decisions regarding the toxicity of this product in overdose. Objective: To compare the pharmacokinetics of Panadol Extend and immediate-release paracetamol (APAP-IR) in simulated overdose model in healthy volunteers. Methods: Cross-over study using a dose of 90 mg/kg ideal body weight of Panadol Extend or APAP-IR in seven healthy volunteers. Serum paracetamol concentrations were measured over 12 h. Maximal paracetamol concentration (Cmax), time to Cmax (Tmax), area under the curve (AUC) and elimination half-life (t1/2) were compared. Results: Mean paracetamol dose was 73 mg/kg actual body weight. Panadol Extend produced lower Cmax (0.208 mmol/L A? 0.02 vs 0.48 mmol/L A? 0.02, P = 0.0001) and AUC0-12h when compared with APAP-IR. Tmax was delayed with Panadol Extend (2.83 h A? 0.26 vs 0.94 h A? 0.17, P = 0.0001). Absorption was complete in all subjects by 4 h post ingestion in both study arms. Elimination t1/2 was 1.69 A? 0.09 h for APAP-IR and 1.65 A? 0.13 h for Panadol Extend (not significant). Conclusions: Reductions in Panadol Extend Cmax and AUC0-12h might be related to elimination occurring during the absorption phase. In this model of Panadol Extend moderate overdose, Tmax was significantly delayed. In larger overdoses, time to peak paracetamol levels might be further delayed, because of continuing absorption from the formulation. Therefore, the paracetamol treatment nomogram might not reliably predict hepatotoxicity from Panadol Extend if paracetamol levels are measured too early. A? 2006 The Authors.
Original languageEnglish
Pages (from-to)398 - 403
Number of pages6
JournalEmergency Medicine Australasia
Volume18
Issue number4
DOIs
Publication statusPublished - 2006
Externally publishedYes

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