Document Detail

Quantifying pain relief following administration of a novel formulation of paracetamol (acetaminophen).
MedLine Citation:
PMID:  20154294     Owner:  NLM     Status:  MEDLINE    
This article describes how a model-based analysis was used to aid development of a novel formulation technology. Paracetamol (acetaminophen) was used as the motivating example with 4 different formulations (2 developmental and 2 commercial) compared using stochastic (Monte Carlo) pharmacokinetic (PK)-pharmacodynamic (PD) simulations to explore potential differences in pharmacodynamic outcomes. PK models were developed from data collected during an intensively sampled, 4-arm crossover trial in 25 fasted healthy subjects, administered 1 g of paracetamol in 4 different formulations. The PK models were linked to a previously published PD model that quantified pain relief over time following tonsillectomy. The number needed to treat (NNT) was the primary numeric used to compare effectiveness. The developmental formulations were likely to produce faster and greater analgesia with an NNT (compared with placebo) to reduce pain by 50% over a 45-minute interval post dose of 2.75 and 2.88 compared with 4.31 and 3.2 for the commercial products. Over the course of 1 hour, all formulations were comparable. The stochastic simulations provided support that the novel formulation technology was likely to provide a clinically meaningful advantage and should be developed further.
Bruce Green; Stephen Chandler; Garth MacDonald; Geraldine Elliott; Michael S Roberts
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Publication Detail:
Type:  Clinical Trial; Clinical Trial, Phase I; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2010-02-12
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  50     ISSN:  1552-4604     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-05     Completed Date:  2011-03-04     Revised Date:  2012-06-06    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1406-13     Citation Subset:  IM    
Model Answers Pty Ltd, Brisbane, Queensland, Australia.
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MeSH Terms
Acetaminophen / administration & dosage*,  blood,  pharmacokinetics,  pharmacology*
Analgesics, Non-Narcotic / administration & dosage*,  blood,  pharmacokinetics,  pharmacology*
Chemistry, Pharmaceutical
Computer Simulation
Cross-Over Studies
Decision Support Techniques
Models, Biological
Models, Statistical
Monte Carlo Method
Pain Measurement / statistics & numerical data*
Pharmaceutic Aids / chemistry
Placebo Effect
Sample Size
Technology, Pharmaceutical
Reg. No./Substance:
0/Analgesics, Non-Narcotic; 0/Pharmaceutic Aids; 103-90-2/Acetaminophen
Comment In:
J Clin Pharmacol. 2012 May;52(5):778; author reply 779   [PMID:  21527400 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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