Drug Design, Development and Therapy (Sep 2019)
The safety, pharmacodynamics, and pharmacokinetics of immediate-release formulation containing esomeprazole 20 mg/sodium bicarbonate 800 mg in healthy adult male
Abstract
Dasohm Kim1,2, Min Soo Park1,2, Byung Won Yoo2, Taegon Hong2, Shin Jung Park3, Choon Ok Kim2 1Department of Pharmaceutical Medicine and Regulatory Sciences, College of Medicine and Pharmacy, Yonsei University, Incheon, Korea; 2Department of Clinical Pharmacology and Clinical Trials Center, Severance Hospital, Yonsei University Health System, Seoul, Korea; 3Chong Kun Dang Research Institute, Chong Kun Dang Pharmaceutical Corporation, Seoul, KoreaCorrespondence: Choon Ok KimDepartment of Clinical Pharmacology and Clinical Trials Center, Severance Hospital, Yonsei University Health System, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, KoreaTel +82 22 228 0455Fax +82 22 227 7890Email [email protected]: Esomeprazole is the most effective treatment for acid-related disorders and is widely used with enteric coating due to rapid degradation in the acidic environment. However, the enteric-coated formulation delays absorption and onset of action. To overcome this limitation, an immediate-release formulation containing esomeprazole 20 mg and sodium bicarbonate 800 mg (IR-ESO) was developed.Purpose: To evaluate the safety, pharmacokinetics (PK), and pharmacodynamics of IR-ESO compared to those of esomeprazole 20 mg (ESO).Methods: A randomized, open-label, multiple-dose, two-treatment, two-sequence crossover study was conducted in 40 healthy male subjects. Subjects received either IR-ESO or ESO for 7 days. After single and multiple dosing, blood samples were collected for PK analysis, and intragastric pH was assessed by 24-hr pH monitoring.Results: Plasma esomeprazole exposure of IR-ESO was similar to that of ESO after single and multiple dosing. Time to peak concentration of IR-ESO (0.50–0.75 hr) was shorter than that of ESO (1.25–1.50 hr). Percentage changes in 24-hr integrated gastric acidity from baseline for IR-ESO were similar to those for ESO. In addition, mean time to maintain gastric pH >4 for 24 hr was similar for both drugs (IR-ESO 55.5–69.9% vs ESO 56.8–70.2%). Evaluation of time to first reach pH 4 after dosing indicated that IR-ESO showed a faster onset than ESO. All subjects found the drug tolerable, and there were no significant differences in adverse events between two drugs.Conclusion: This study showed that IR-ESO produced a rapid, safe and sustained gastric acid suppression (ClinicalTrials.gov: NCT03211143).Keywords: sodium bicarbonate, immediate-release esomeprazole, esomeprazole, 24-hr pH monitoring
