Understanding synergy.
Am J Physiol Endocrinol Metab
; 304(3): E237-53, 2013 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-23211518
ABSTRACT
Analysis of the interactive effects of combinations of hormones or other manipulations with qualitatively similar individual effects is an important topic in basic and clinical endocrinology as well as other branches of basic and clinical research related to integrative physiology. Functional, as opposed to mechanistic, analyses of interactions rely on the concept of synergy, which can be defined qualitatively as a cooperative action or quantitatively as a supra-additive effect according to some metric for the addition of different dose-effect curves. Unfortunately, dose-effect curve addition is far from straightforward; rather, it requires the development of an axiomatic mathematical theory. I review the mathematical soundness, face validity, and utility of the most frequently used approaches to supra-additive synergy. These criteria highlight serious problems in the two most common synergy approaches, response additivity and Loewe additivity, which is the basis of the isobole and related response surface approaches. I conclude that there is no adequate, generally applicable, supra-additive synergy metric appropriate for endocrinology or any other field of basic and clinical integrative physiology. I recommend that these metrics be abandoned in favor of the simpler definition of synergy as a cooperative, i.e., nonantagonistic, effect. This simple definition avoids mathematical difficulties, is easily applicable, meets regulatory requirements for combination therapy development, and suffices to advance phenomenological basic research to mechanistic studies of interactions and clinical combination therapy research.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sistema Endocrino
/
Metabolismo Energético
/
Homeostasis
/
Hormonas
/
Modelos Biológicos
Tipo de estudio:
Prognostic_studies
/
Qualitative_research
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Am J Physiol Endocrinol Metab
Asunto de la revista:
ENDOCRINOLOGIA
/
FISIOLOGIA
/
METABOLISMO
Año:
2013
Tipo del documento:
Article