PII-107 - COMPARATIVE PHARMACOKINETICS/PHARMACODYNAMICS OF FIXED-DOSE COMBINATION OF RABEPRAZOLE/MAGNESIUM OXIDE 10/350MG (DHNP-2001A) TO THE CONVENTIONAL ENTERIC-COATED RABEPRAZOLE 10MG

S. Lee, H. Won, J. Khwarg, S. Goh, S. Lee; Seoul National University Hospital.

Background: DHNP-2001A is a novel fixed-dose combination (FDC) of rabeprazole/magnesium oxide (MgO) 10/350 mg developed for rapid release of rabeprazole to exert potent inhibitory effects on acid secretion through gastric pH neutralization. This study aimed to compare the pharmacokinetics (PKs) and pharmacodynamics (PDs) of DHNP-2001A and conventional enteric-coated rabeprazole.

Methods: A randomized, open-label, multiple-dose, crossover study was conducted. Subjects were administered oral doses of the test drug, FDC of rabeprazole/MgO 10/350 mg (DHNP-2001A), or the reference drug, rabeprazole sodium 10 mg (Pariet®), for 7-consecutive days in each period with a 14-day washout. Serial blood samples were collected for PK assessment and the PK parameters were estimated using non-compartmental analyses. Continuous 24-hour intragastric pH monitoring was done for PD assessment. Geometric mean ratios (GMRs) and 90% confidence intervals (Cls) of DHNP-2001A to the conventional rabeprazole after multiple-dose was calculated for the PK and PD parameters.

Results: Thirty-nine healthy subjects completed the study. The overall pharmacokinetic characteristics of DHNP-2001A were similar to those of the conventional rabeprazole except for the absorption period. The absorption of the rabeprazole was faster in the DHNP-2001A with the Tmax ranging from 1.00 to 2.50 hours, whereas the conventional rabeprazole ranged from 2.00 to 8.00 hours. The GMR (90% CI) of the area under the curve within a dosing interval (τ) at steady state (AUCτ,ss) was 0.9606 (0.8919 – 1.0345). After the single and multiple administration of the DHNP-2001A, the extent of gastric acid suppression was similar to the conventional rabeprazole. The GMR (90% CI) of DHNP-2001A to the conventional rabeprazole for percent decrease from baseline in the integrated gastric acidity over a 24-hour period was 1.0043 (0.8829 – 1.1424). Also, DHNP-2001A showed rapid suppression of gastric acid compared to the reference drug.

Conclusion: The fixed-dose combination of rabeprazole/MgO 10/350 mg (DHNP-2001A) showed faster absorption and rapid gastric acid suppression with a similar systemic exposure of rabeprazole compared to the conventional enteric-coated rabeprazole.