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Volume 19
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10.3390/ph19060815
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Article

A Genetic Algorithm-Based Approach for Quantitative Prediction of Drug-Drug Interactions Caused by Cytochrome P450 3A Inhibition or Induction in Horses

by
Veronica Di Paolo
1,*,
Francesco Maria Ferrari
2,
Italo Poggesi
3,
Mauro Dacasto
1,
Luigi Quintieri
4 and
Francesca Capolongo
1
1
Department of Comparative Biomedicine and Food Science, University of Padua, Viale dell’Università 16, 35020 Legnaro, Italy
2
Department of Research and Development, MeteRSit, 35129 Padua, Italy
3
Quantitative Clinical Pharmacology, GSK, 37135 Verona, Italy
4
Laboratory of Drug Metabolism, Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35121 Padua, Italy
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2026, 19(6), 815; https://doi.org/10.3390/ph19060815
Submission received: 3 April 2026 / Revised: 6 May 2026 / Accepted: 19 May 2026 / Published: 22 May 2026
(This article belongs to the Section Pharmacology)
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Abstract

Introduction: A genetic algorithm (GA)-based approach was designed to predict drug–drug interactions (DDIs) triggered by cytochrome P450 3A (CYP3A) inhibition or induction in horses. Methods: Area under the concentration-time curve ratios (AUCRs), obtained from published in vivo DDI studies in horses, were used to compute the following parameters: (1) the contribution ratio (CR), i.e., the fraction of the substrate dose metabolized via the CYP3A pathway, and (2) the interacting drug’s inhibitory potency or inducing efficacy (IR or IC, respectively). Results: AUCRs for 9 substrates, 12 inhibitors, and 1 inducer of equine CYP3A were predicted and validated with the developed method. More than 96% of predictions fell within the commonly accepted range of 50–200% of observed values. Conclusions: The proposed GA-based method may be a useful tool to estimate possible clinically relevant DDIs when co-administration of a CYP3A substrate and a CYP3A-interacting drug is anticipated.
Keywords: drug–drug interactions; cytochrome P450 3A; genetic algorithm; equine drug–drug interactions; cytochrome P450 3A; genetic algorithm; equine
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MDPI and ACS Style

Di Paolo, V.; Ferrari, F.M.; Poggesi, I.; Dacasto, M.; Quintieri, L.; Capolongo, F. A Genetic Algorithm-Based Approach for Quantitative Prediction of Drug-Drug Interactions Caused by Cytochrome P450 3A Inhibition or Induction in Horses. Pharmaceuticals 2026, 19, 815. https://doi.org/10.3390/ph19060815

AMA Style

Di Paolo V, Ferrari FM, Poggesi I, Dacasto M, Quintieri L, Capolongo F. A Genetic Algorithm-Based Approach for Quantitative Prediction of Drug-Drug Interactions Caused by Cytochrome P450 3A Inhibition or Induction in Horses. Pharmaceuticals. 2026; 19(6):815. https://doi.org/10.3390/ph19060815

Chicago/Turabian Style

Di Paolo, Veronica, Francesco Maria Ferrari, Italo Poggesi, Mauro Dacasto, Luigi Quintieri, and Francesca Capolongo. 2026. "A Genetic Algorithm-Based Approach for Quantitative Prediction of Drug-Drug Interactions Caused by Cytochrome P450 3A Inhibition or Induction in Horses" Pharmaceuticals 19, no. 6: 815. https://doi.org/10.3390/ph19060815

APA Style

Di Paolo, V., Ferrari, F. M., Poggesi, I., Dacasto, M., Quintieri, L., & Capolongo, F. (2026). A Genetic Algorithm-Based Approach for Quantitative Prediction of Drug-Drug Interactions Caused by Cytochrome P450 3A Inhibition or Induction in Horses. Pharmaceuticals, 19(6), 815. https://doi.org/10.3390/ph19060815

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