DISCUSSION
heartburn
ACID INDIGESTION, DRUG-DRUG INTERACTION
Aluminum hydroxide/magnesium hydroxide is an over-the-counter non-systemic antacid commonly used in the general population to relieve heartburn, acid indigestion, and sour stomach. The change in gastric pH is achieved by neutralizing secreted gastric acid rather than inhibiting the secretion of the acid (Omeprazole is a PPI that blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion, irrespective of the stimulus (PPIs suppress gastric acid secretion to a greater extent for a longer duration than some other gastric pH-elevating agents, such as H2 blockers (e.g., famotidine) and antacids. As both antacids and PPIs are commonly used in clinical practice, the PPI omeprazole was selected for evaluation in this study, as any potential effect on TBP PK was likely to be maximized with the co-administration of a PPI. Aluminum hydroxide/magnesium hydroxide/simethicone is a short-acting acid-neutralizing agent, while PPIs inhibit the H+/K+ ATPase pump irreversibly with an effect that lasts approximately 7 to 10 days after discontinuation. As such, a fixed sequence design was selected where PPI dosing was conducted during the last dosing period of the study.The washout period of 7 days between dosing periods was considered sufficient to prevent carryover effects of the preceding treatment, based on TBP tA previous study performed with a pediatric granule formulation of tebipenem (Orapenem) marketed in Japan demonstrated a reduction in TBP Cmax by 44% to 63% and AUCCoadministration of either a single dose of aluminum hydroxide/magnesium hydroxide/simethicone or multiple doses of omeprazole with a single dose of TBP-PI-HBr had varying effects on Cmax and AUC. TBP AUC was approximately 11% lower for TBP-PI-HBr in combination with aluminum hydroxide/magnesium hydroxide/simethicone or omeprazole, as compared with TBP-PI-HBr alone. However, TBP plasma Cmax decreased by 22% and 43% when TBP-PI-HBr was co-administered with a single dose of aluminum hydroxide/magnesium hydroxide/simethicone or with omeprazole QD for 5 days, respectively. While geometric mean TBP Cmax were higher for TBP-PI-HBr alone, slight delay in TBP TIn summary, the study results confirm no clinically meaningful drug-drug interaction with co-administration of TBP-PI-HBr and omeprazole or aluminum hydroxide/magnesium hydroxide/simethicone.