Acidifying agents impact erlotinib and gefitinib pharmacokinetic parameters and elevate liver enzymes in Wistar rats.

Erlotinib (ERL) and Gefitinib (GEF) are weakly basic drugs with pH-dependent solubility profiles mainly dependent on stomach pH. We proposed possible drug and/or food-drug interactions with acidifying agents. Citric acid (CA) and phosphoric acid (PPA) are the most common acidifying agents used in food and medication to treat certain conditions. This study evaluated the impact of concomitant consumption of CA and PA on ERL and GEF pharmacokinetic parameters (PKs). The PKs of ERL and GEF were investigated in rats after four weeks of CA and PPA consumption in low (175 mg/kg) and high (100 mg/kg) doses using UPLC-MS/MS. Data indicated that acidifying agents altered PKs of ERL and GEF dose-dependently. High doses of CA and PPA significantly increased the Cmax of ERL by 103% and 218%, the AUC0-72 by 35% and 78%, respectively, while reducing CL/F by 44% with CA and 74% with PPA. For GEF, Low and high doses of PPA increased Cmax and Tmax with a reduction of CL/F. A low dose of CA did not impact Cmax, significantly decreased AUC0-72 (28%), and increased CL/F (16%). The high dose of CA increased Cmax (13%) with no impact on AUC0-72 and decreased CL/F (23%). Furthermore, both doses of acidifying agents significantly increased liver enzyme levels and reduced body weight within two weeks. The results demonstrated that the PKs of both drugs were changed, and caution and close monitoring should be taken with ERL and GEF when co-administered with an acidifying agent.