Population pharmacokinetics of erlotinib in patients with non-small cell lung cancer (NSCLC): A model-based meta-analysis.

Background: Erlotinib is a potent first-generation epidermal growth factor receptor tyrosine kinase inhibitor. Due to its proximity to the upper limit of tolerability, dose adjustments are often necessary to manage potential adverse reactions resulting from its pharmacokinetic (PK) variability.

Methods: Population PK studies of erlotinib were identified using PubMed databases. Simulations of erlotinib concentrations were conducted at 4-h intervals, with covariate simulations based on patient characteristics.

Results: Three studies were included in this analysis. The one-compartment model was determined to be the most suitable for describing the population PK of erlotinib. A decrease in clearance was observed with age, while an increase in clearance was noted in smoking patients. The volume of distribution was positively correlated with body weight. Our study proposes optimal dosing of erlotinib based on age and smoking status, categorizing the patient population into six groups.

Conclusion: This is the first report on a model-based meta-analysis approach to develop a population PK model of erlotinib in patients with non-small cell lung cancer. Our findings suggest that an increased dosage is appropriate for patients under 60 who smoke, whereas a reduced dosage is more suitable for non-smoking older patients.