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Comparison of null models for combination drug therapy reveals Hand model as biochemically most plausible.

Sci. Rep. 9:3002 (2019)
Verlagsversion Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag
Null models for the effect of combination therapies are widely used to evaluate synergy and antagonism of drugs. Due to the relevance of null models, their suitability is continuously discussed. Here, we contribute to the discussion by investigating the properties of five null models. Our study includes the model proposed by David J. Hand, which we refer to as Hand model. The Hand model has been introduced almost 20 years ago but hardly was used and studied. We show that the Hand model generalizes the principle of dose equivalence compared to the Loewe model and resolves the ambiguity of the Tallarida model. This provides a solution to the persisting conflict about the compatibility of two essential model properties: the sham combination principle and the principle of dose equivalence. By embedding several null models into a common framework, we shed light in their biochemical validity and provide indications that the Hand model is biochemically most plausible. We illustrate the practical implications and differences between null models by examining differences of null models on published data.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Isobolographic Analysis; Partial Agonist; Lung-cancer; Synergy; Inhibition; Full
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 9, Heft: 1, Seiten: , Artikelnummer: 3002 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed