Pharmacokinetics and Pharmacodynamics of a Fixed-Dose Combination of Esomeprazole and Magnesium Hydroxide Compared to the Enteric-Coated Esomeprazole

• Published in: Clinical therapeutics Vol. 46; no. 11; pp. 870 - 876
• Main Authors: Kim, Yoonjin, Bae, Sungyeun, Jeon, Inseung, Kwon, Jihoon, Hong, Sung Hee, Kim, Na Young, Yu, Kyung-Sang, Jang, In-Jin, Lee, SeungHwan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2024; Elsevier Limited
• Subjects: Acidity; Acids; Adult; Adults; Antacids; Antacids - administration & dosage; Antacids - pharmacology; Catheters; Coatings; Comparative pharmacokinetics/pharmacodynamics; Cross-Over Studies; Drug Combinations; Drug development; Drug dosages; Esomeprazole - administration & dosage; Esomeprazole - pharmacokinetics; Esomeprazole - pharmacology; Esophagus; Female; Gastric juice; Gastroesophageal reflux; Gastroesophageal reflux disease; Healthy Volunteers; Humans; Immediate release; Internal Medicine; Magnesium; Magnesium Hydroxide - administration & dosage; Male; Middle Aged; Omeprazole; Pharmacodynamics; Pharmacokinetics; Proton pump inhibitors; Proton Pump Inhibitors - administration & dosage; Proton Pump Inhibitors - pharmacokinetics; Proton Pump Inhibitors - pharmacology; Tablets, Enteric-Coated; Young Adult; Comparative pharmacokinetics/pharmacodynamics; Immediate release; GERD; TEAE; FDC; Gastroesophageal reflux disease; PPI; BMI; body mass index; treatment-emergent adverse event; fixed-dose combination; proton pump inhibitor
• ISSN: 0149-2918; 1879-114X; 1879-114X
• DOI: 10.1016/j.clinthera.2024.08.006

•Newly developed esomeprazole/magnesium hydroxide fixed-dose combination (FDC) exhibits faster time to reach maximum concentration compared to enteric-coated esomeprazole.•The FDC demonstrates a shorter time to achieve gastric pH ≥ 4, indicating more rapid and effective acid suppression compared to enteric-coated esomeprazole.•Comparable systemic exposure and decrease in integrated gastric acidity over 24 hours highlight equivalent inhibition of gastric acid secretion between the FDC and enteric-coated esomeprazole.•The esomeprazole/magnesium hydroxide FDC presents as a promising option with faster absorption and effective gastric acid suppression, offering potential clinical advantages over enteric-coated esomeprazole. A fixed-dose combination (FDC) of proton pump inhibitors (PPIs) and antacid salts enables rapid acid suppression through the neutralizing effect of the antacid salt and the rapid absorption of PPIs. This study aimed to compare the pharmacokinetics (PKs) and pharmacodynamics (PDs) of a recently formulated FDC of esomeprazole and magnesium hydroxide to the enteric-coated esomeprazole in healthy subjects. A randomized, open-label, multiple-dose, two-treatment, two-way crossover design was conducted in healthy subjects. Forty-nine subjects were randomized to one of the two treatment sequences and received either the test drug (esomeprazole/magnesium hydroxide 40/350 mg) or reference drug (enteric-coated esomeprazole 40 mg) for 7 days in the first period and the alternative in the second period with a 14-day washout period. Blood samples were collected for up to 24 hours for PK assessment, and 24-hour gastric pH monitoring was conducted for PD assessment both before and after a single administration, as well as at a steady state after seven consecutive days of administration. The PK and PD parameters were compared between the two drugs. After multiple administrations, the median value of time to reach maximum concentration was faster in the test drug than in the reference drug, with a difference of 1.68 hours. The overall systemic exposure of the test drug was similar to that of the reference drug, and the PK parameter fell within the equivalence criteria. The test drug demonstrated a shorter time to reach gastric pH ≥ 4 compared to the reference drug (P = 0.0463). A decrease from baseline in integrated gastric acidity over 24 hours, which represents the degree of inhibition of gastric acid secretion, was equivalent between the two drugs. The fixed-dose combination of esomeprazole and magnesium hydroxide showed rapid absorption and quicker gastric acid suppression than enteric-coated esomeprazole with comparable PK and PD properties. ClinicalTrials.gov identifier: NCT04324905 (https://classic.clinicaltrials.gov/ct2/show/NCT04324905).