Introduction: Erlotinib's gastrointestinal solubility and absorption are decreased by proton pump inhibitors (PPIs). Since erlotinib is a lipophilic drug, we hypothesized that concomitant intake with the fatty beverage milk may be a feasible way to increase erlotinib uptake. We performed a two-period, randomized, crossover study to investigate the influence of cow's milk with 3.9% fat on the exposure of erlotinib with and without the PPI esomeprazole in patients with non-small cell lung cancer (NSCLC). The effect of esomeprazole was studied in an additional intrapatient comparison.
Method: Pharmacokinetic sampling was performed on days 7 and 14 during 24 consecutive hours. During the 7 days prior to pharmacokinetic sampling, erlotinib was taken daily with 250 mL of either water or milk. In the PPI arm, esomeprazole (40 mg once daily 3 h prior to erlotinib) was taken for 3 days.
Results: Erlotinib area under the curve from time zero to 24 h (AUC24) did not significantly change when administered with milk, compared with water, in both non-PPI users (n = 14; - 3%; 95% confidence interval [CI] - 12 to 8%; p = 0.57) and patients who used esomeprazole (n = 15; 0%; 95% CI - 15 to 17%; p = 0.95). Esomeprazole decreased erlotinib AUC24 by 47% (n = 9; 95% CI - 57 to - 34%; p < 0.001) and Cmax by 56% (95% CI - 64 to - 46%; p < 0.001). No differences in toxicities were observed between milk and water.
Conclusion: Milk with 3.9% fat has no effect on the exposure to erlotinib in NSCLC patients, independent of PPI use. The combination with milk is safe and well tolerated. Concomitant esomeprazole treatment strongly decreased both erlotinib AUC24 and Cmax and should be avoided if possible.