Explaining the acetaminophen-ibuprofen analgesic interaction using a response surface model

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dc.contributor.author Sturge, Jacqueline en
dc.contributor.author Anderson, BJ en
dc.date.accessioned 2015-07-28T02:31:26Z en
dc.date.available 2011-05-31 en
dc.date.issued 2011-12 en
dc.identifier.citation Pediatric Anesthesia, 2011, 21 (12), pp. 1234 - 1240 (7) en
dc.identifier.issn 1155-5645 en
dc.identifier.uri http://hdl.handle.net/2292/26468 en
dc.description.abstract Background:  The value of acetaminophen–ibuprofen combination therapy over single therapy is uncertain in acute pediatric pain management. A model describing the interaction between these two drugs would be useful both for understanding current literature and for future study design. Methods:  Published pooled time–effect profiles in adults given combination or single therapy after dental extraction were used to construct an interaction model. Pain was measured using pain intensity differences (PRID, 0–10) from zero to eight hours postoperatively. Pharmacodynamic parameter estimates were assumed the same in adults as children. Pediatric pharmacokinetic estimates were scaled using allometric theory. Curve fitting was performed using nonlinear mixed effects models. Results:  Pooled data were available in adults given eight single and multiple dose combinations as well as placebo. The ibuprofen dose range was 100–400 mg, and acetaminophen dose range was 500–1000 mg. Pharmacodynamic parameter estimates, expressed using the Hill equation, were maximum effect (EMAX) 4.06 (95% CI: 3.24, 5.51), the concentration of acetaminophen associated with 50% of the maximal drug effect (EC50,ACET) 11.9 (95% CI: 6.0, 49.5) mg·l−1, the ibuprofen EC50 (EC50,IBU) 5.07 (95% CI: 3.50, 8.26) mg·l−1, and Hill coefficient 2 (95% CI: 1.3, 2.8). An interaction term was fixed at zero (additive interaction). Simulation showed that the addition of acetaminophen to ibuprofen when less than 5 mg·kg−1 was effective; acetaminophen had minimal effect when given with ibuprofen at doses greater than 5 mg·kg−1 in the immediate postoperative period. A more sustained analgesic effect was noted at 4–8 h after combination dosing. Conclusions:  This drug interaction modeling example is useful to explain combination therapy nuances and impacts on study design. Differences in effect between single drug therapy and combination therapy should be sought at lower doses and beyond the immediate postoperative period. Combination therapy may prolong the duration of analgesia. The maximum effect (EMAX) limits the early additional analgesic gain from combination therapy beyond commonly used doses. en
dc.language English en
dc.publisher John Wiley & Sons en
dc.relation.ispartofseries Pediatric Anesthesia en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/1155-5645/ http://olabout.wiley.com/WileyCDA/Section/id-820227.html en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Explaining the acetaminophen-ibuprofen analgesic interaction using a response surface model en
dc.type Journal Article en
dc.identifier.doi 10.1111/j.1460-9592.2011.03644.x en
pubs.issue 12 en
pubs.begin-page 1234 en
pubs.volume 21 en
dc.rights.holder Copyright: John Wiley & Sons en
pubs.author-url http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9592.2011.03644.x/abstract en
pubs.end-page 1240 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Article en
pubs.elements-id 245345 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Pharmacology en
dc.identifier.eissn 1460-9592 en
pubs.record-created-at-source-date 2012-10-09 en


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