pH-dependent drug interactions with acid reducing agents

Gastric acid reducing agents (ARAs) are drugs used for treating peptic ulcer disease. The higher gastric pH caused by ARAs can decrease solubility and absorption of the drugs co-administered with ARAs. The study examines the relationship between solubility and pharmacokinetic (PK) changes of cancer drugs concurrently used with ARAs, and the subsequent dose adjustment of cancer drugs to account for drug interactions. We hypothesize that (1) cancer drugs with pH-dependent solubility are evaluated more for drug interactions with ARAs, as compared to those with pH-independent solubility, (2) a decrease in the area-under-the-concentration curve (AUC) and maximum drug concentration (C_max), the PK measurements indicative of drug absorption, is observed more in drugs with pH-dependent solubility that sharply decreases at pH 3-5, and (3) dose adjustment is recommended more for drugs with a ≥45% decrease in AUC and C_max . The results showed no significant difference in the proportions of drugs where drug interactions were evaluated between drugs with pH-dependent solubility versus those with pH-independent solubility. A decrease in AUC and C max was observed more in drugs with pH- dependent solubility that sharply decreased at pH 3-5 than those without such property (50% vs. 0%; p=0.04). Dose adjustment was recommended more for drugs with a ≥45% decrease in AUC and C_max than for those with a <45% decrease or no change (100% vs. 0%; p=0.002). These findings may help identify drugs with a higher risk of drug interactions with ARAs and assess the need for comprehensive evaluation of drug interactions and dose adjustment.