Pharmacokinetic interaction between pyrotinib and loperamide

The term Pharmacokinetic interaction between pyrotinib and loperamide refers to the pharmacological relationship and potential drug-drug interaction (DDI) between the tyrosine kinase inhibitor pyrotinib and the antidiarrheal agent loperamide. Pyrotinib is an irreversible pan-ErbB receptor tyrosine kinase inhibitor used primarily in the treatment of HER2-positive metastatic breast cancer (Zhu et al., 2020). Diarrhea is the most common adverse event associated with pyrotinib treatment, frequently requiring the administration of loperamide for symptom management. Loperamide is a substrate of the efflux transporter P-glycoprotein (P-gp), which normally limits its absorption and prevents it from crossing the blood-brain barrier (Wandel et al., 2002). Pyrotinib has been identified as an inhibitor of P-gp and Breast Cancer Resistance Protein (BCRP), which can lead to increased systemic exposure of loperamide when the two drugs are co-administered. Clinical studies have investigated this interaction to ensure that the use of loperamide to manage pyrotinib-induced diarrhea does not result in opioid-like central nervous system toxicity. Consequently, this entry represents a clinical safety and pharmacokinetic profile rather than a specific therapeutic target or molecular entity.

Other names

Pyrotinib-loperamide interactionDrug-drug interaction between pyrotinib and loperamide

Pyrotinib acts as an inhibitor of the efflux transporter P-glycoprotein (P-gp), which can increase the systemic exposure and central nervous system penetration of loperamide, a P-gp substrate.