PMID: 8606615Jan 1, 1996Paper

Testing for synergism over a range of fixed ratio drug combinations: replacing the isobologram

Life Sciences
Ronald J Tallarida, Robert Raffa

Abstract

An isobologram is a Cartesian plot of pairs of doses that, in combination, yield a specified level of effect. It is a convenient and presently popular way of graphically displaying results of drug-combination and similar studies, because paired values of experimental points that fall below or above the line connecting the axial points (usually ED50 values) denote supra- and sub-additive combinations, respectively. However, an isobologram does not fulfill the criteria for standard least squares regression analysis. It is thus less useful for addressing questions related to the range of combination ratios over which synergy occurs. We describe herein a substitute for the isobologram in which log(total-dose) is plotted against the proportion of a component in a combination. One advantage is that a nonlinear curve-fitting procedure and determination of the confidence interval of a single parameter allow the determination of departure from additivity over a range of fixed proportion mixtures. An example is given of the combination of two analgesics (acetaminophen and tramadol hydrochloride). Another advantage of the new method is the reduction of animal use.

Citations

Jan 1, 2014·Environmental Toxicology and Pharmacology·Agnieszka MarczakAneta Rogalska
Jul 22, 1999·European Journal of Pharmacology·J D Roth, N E Rowland
Jan 18, 2012·International Journal of Obesity : Journal of the International Association for the Study of Obesity·S ZhaoM R Hayes
May 15, 2001·Journal of Clinical Pharmacy and Therapeutics·R B Raffa
Aug 9, 2001·Journal of Clinical Pharmacy and Therapeutics·R B Raffa
Apr 19, 2012·The Journal of Pharmacology and Experimental Therapeutics·Ronald J Tallarida
Jun 28, 2012·Genes & Cancer·Ronald J Tallarida
Oct 12, 2012·Journal of Pain Research·Joseph V PergolizziRobert B Raffa
Feb 17, 2010·The Consultant Pharmacist : the Journal of the American Society of Consultant Pharmacists·Michael NamakaHoward Intrater
Aug 21, 2013·Biochemical Pharmacology·Terry Kenakin, Michael Williams
May 3, 2012·Pain Research and Treatment·Aldric Hama, Jacqueline Sagen
May 5, 2011·Pain Medicine : the Official Journal of the American Academy of Pain Medicine·Anton KolosovColin S Goodchild
Feb 4, 2012·Journal of Pharmacological Sciences·Víctor Fernández-DueñasFrancisco Ciruela
Mar 10, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hao YinWeihong He
Oct 22, 2002·The Journal of Pharmacology and Experimental Therapeutics·Elizabeth A BolanGavril W Pasternak
Sep 11, 2003·The Journal of Pharmacology and Experimental Therapeutics·Ronald J TallaridaRobert B Raffa
Mar 21, 2016·Current Protocols in Pharmacology·Ronald J Tallarida
Jul 3, 2020·Biological & Pharmaceutical Bulletin·Kazumi YoshizawaTakehisa Hanawa
Apr 5, 2013·Journal of Clinical Pharmacy and Therapeutics·R J TallaridaZ Obradovic
Mar 27, 2010·The Journal of Pain : Official Journal of the American Pain Society·Robert B RaffaRonald J Tallarida

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