Eur J Drug Metab Pharmacokinet. 2025 Feb 16. doi: 10.1007/s13318-025-00937-4. Online ahead of print.
ABSTRACT
BACKGROUND AND OBJECTIVE: Atorvastatin is dosed in its active acid form although it exists in equilibrium with its inactive lactone form in vivo. Although in vitro atorvastatin acid displays pH-dependent conversion to the lactone metabolite, pharmacokinetic (PK) data on the effect of elevated gastric pH on atorvastatin and major atorvastatin-related species are not currently available. In this dedicated study, we investigated the effect of food and acid-reducing agents on the PK of atorvastatin and its three major metabolites in humans.
METHODS: This was an open label, randomized, crossover study conducted in 17 healthy volunteers. Part 1 examined the PK of a 10-mg dose of atorvastatin co-administered with or without a 600-mg dose of sodium bicarbonate in fasted and fed states. Part 2 was a single assessment to examine the PK of a 10-mg dose of atorvastatin in the fasted state following a 5-day treatment course of 40-mg daily esomeprazole. Gastric pH was monitored during treatments using Heidelberg capsules. A linear mixed effects model was used to derive ratios for PK parameters of atorvastatin and metabolites between treatments.
RESULTS: Similar to previous food effect studies, food significantly decreased the maximum concentration (Cmax) and increased the time to Cmax (tmax) of atorvastatin, with minimal effect on total exposure of atorvastatin or metabolites. Neither sodium bicarbonate, in the fed or fasted state, nor treatment with esomeprazole had a clinically meaningful effect on the exposure of atorvastatin or its metabolites.
CONCLUSIONS: According to these results, atorvastatin PK does not appear to be sensitive to changes in gastric pH.
PMID:39956861 | DOI:10.1007/s13318-025-00937-4
