RESEARCH PAPER
Two isobolographic approaches in the evaluation of drug-drug interaction for non-parallel concentration-response curves in an in vitro study
1
Department of Occupational Medicine, Medical University, Lublin, Poland
2
Department of Paediatric Cardiology, Medical University, Lublin, Poland
3
Department of Family Medicine and Geriatric Nursing, Medical University, Lublin, Poland
4
Department of Paediatrics and Gastroenterology, Medical University, Lublin, Poland
5
Clinic of Anaesthesiology and Paediatric Intensive Care, Medical University, Lublin, Poland
Corresponding author
Jarogniew J. Łuszczki
Department of Occupational Medicine, Medical University of Lublin, 20-090, Lublin, Poland
Department of Occupational Medicine, Medical University of Lublin, 20-090, Lublin, Poland
J Pre Clin Clin Res. 2025;19(3):91-95
KEYWORDS
TOPICS
ABSTRACT
Introduction and objective:
In in vitro cell line studies, two isobolographic analysis approaches are commonly used when assessing interactions between drugs. Both – the log-probit accompanied with Tallarida method and Chou-Talalay-Martin method – can distinguish pharmacodynamic types of interactions occurring between drugs.
Material and methods:
The aim of the study is to assess the interaction between LY-2183240 and mitoxantrone in the malignant melanoma SK-MEL28 cell line in the MTT assay, by means of two methods – isobolographic (log-probit) accompanied by the Tallarida and Chou-Talalay-Martin method.
Results:
Log-probit accompanied by the Tallarida method revealed that LY-2183240 and mitoxantrone had non-parallel concentration-response curves, and produced an additive interaction in the SK-MEL28 cell line in the MTT assay. In contrast, the Chou-Talalay-Martin method showed that the combination of LY-2183240 and mitoxantrone exerted a synergistic interaction with a combination index value of 0.354.
Conclusions:
The observed discrepancy in the types of interactions between LY-2183240 and mitoxantrone in both methods resulted from the lack of assessment of mutual parallelism of the drugs concentrations-response curves in the Chou-Talalay-Martin method. The utmost caution is advised when utilizing the Chou-Talalay-Martin method in the detection of interactions in in vitro studies, especially for the combinations of drugs with non-parallel concentration-response curves.
In in vitro cell line studies, two isobolographic analysis approaches are commonly used when assessing interactions between drugs. Both – the log-probit accompanied with Tallarida method and Chou-Talalay-Martin method – can distinguish pharmacodynamic types of interactions occurring between drugs.
Material and methods:
The aim of the study is to assess the interaction between LY-2183240 and mitoxantrone in the malignant melanoma SK-MEL28 cell line in the MTT assay, by means of two methods – isobolographic (log-probit) accompanied by the Tallarida and Chou-Talalay-Martin method.
Results:
Log-probit accompanied by the Tallarida method revealed that LY-2183240 and mitoxantrone had non-parallel concentration-response curves, and produced an additive interaction in the SK-MEL28 cell line in the MTT assay. In contrast, the Chou-Talalay-Martin method showed that the combination of LY-2183240 and mitoxantrone exerted a synergistic interaction with a combination index value of 0.354.
Conclusions:
The observed discrepancy in the types of interactions between LY-2183240 and mitoxantrone in both methods resulted from the lack of assessment of mutual parallelism of the drugs concentrations-response curves in the Chou-Talalay-Martin method. The utmost caution is advised when utilizing the Chou-Talalay-Martin method in the detection of interactions in in vitro studies, especially for the combinations of drugs with non-parallel concentration-response curves.
FUNDING
Łuszczki JJ, Błaszkiewicz-Tyniec A, Gałęziowska E, Kowalik A, Krajewska I. Two isobolographic approaches in evaluation of drug-drug
interaction for non-parallel concentration-response curves in an in vitro study. J Pre-Clin Clin Res. 2025;19(3):91–95. doi:10.26444/jpccr/210907
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