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Quantifying Pain Relief Following Administration of a Novel Formulation of Paracetamol (Acetaminophen)
Author(s) -
Green Bruce,
Chandler Stephen,
MacDonald Garth,
Elliott Geraldine,
Roberts Michael S.
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009359181
Subject(s) - acetaminophen , medicine , placebo , crossover study , number needed to treat , pharmacodynamics , pharmacokinetics , anesthesia , confidence interval , pain relief , pharmacology , relative risk , alternative medicine , pathology
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.