Response to Tutorial Drug–Drug Interactions by EM Sellers
Abstract
The authors thank Dr. Sellers for his commentary [1] on the drug–drug interaction (DDI) Tutorial [2]. The authors agree, in general, that evaluation of pharmacokinetic DDIs does not explain all DDIs, but pharmacokinetic DDIs significantly improve dosing recommendations for new drugs (Table 1). The authors also agree that standard population studies do not always reflect the true risk or nature of DDIs in specific subgroups. Pharmacodynamic DDIs, which can be synergistic, additive, or antagonistic, are extremely important [3-5], typically specific for a therapeutic area (e.g., antiviral, pain, oncology) and can lead to unpredictable clinical outcomes. DDIs for biologics are due to the mechanism of action or modulation of disease pathophysiology [4]. While pharmacodynamic and disease-specific interactions remain important, the approach to pharmacokinetic DDIs outlined in the Tutorial offers a robust scientific rationale, reflecting advances in our understanding of metabolizing enzymes and transporters. This information enables the development of sound dosing recommendations for DDIs across therapeutic areas (Table 1). Additionally, scientists should consider DDIs related to the underlying disease or therapeutic area. Dr. Sellers notes that patients are the true “victims” and doctors are the true “perpetrators” of DDIs; the authors agree that clinicians need additional training on the management of complex DDIs to decrease adverse events. The authors believe that the terms…
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