Effect of diammonium glycyrrhizinate on pharmacokinetics of omeprazole by regulating cytochrome P450 enzymes and plasma protein binding rate

Abstract

1. In clinical practice, diammonium glycyrrhizinate is usually used with omeprazole in patients with viral hepatitis and cirrhosis accompanied by peptic ulcers. However, the drug interaction between diammonium glycyrrhizinate and omeprazole remains unclear.

2. In this study, the effects of diammonium glycyrrhizinate on the pharmacokinetics of omeprazole was investigated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method. Male Sprague–Dawley rats were randomly assigned to two groups: omeprazole and omeprazole + diammonium glycyrrhizinate, and the main pharmacokinetic parameters were estimated after oral administration. It was found that using the omeprazole along with the diammonium glycyrrhizinate increased the AUC, AUMC, C_max for omeprazole.

3. For this reason, we used the LC-MS/MS to detect the binding rate of plasma protein (BRPP) of omeprazole in rats, it was found that diammonium glycyrrhizinate could decrease the BRPP in rats. In addition, we found that diammonium glycyrrhizinate specifically inhibited the enzyme activity of the CYP2C19 and CYP3A4, which are involved in the metabolism of the omeprazole.

4. These results mean that diammonium glycyrrhizinate could inhibit the metabolism and increase the plasma concentration of the omeprazole in rats. Overall, diammonium glycyrrhizinate can influence the pharmacokinetics of omeprazole by inhibiting CYP2C19 and CYP3A4 activities and decreasing BRPP of omeprazole.

Keywords:

• Diammonium glycyrrhizinate
• omeprazole
• LC-MS/MS
• cytochrome P450 enzyme
• drug interaction

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This project was financially supported by the Fund of Beijing Medical and Health Foundation [YWJK JJHK YJJ-A711, B17536] and the Fund of Shanghai Pharmaceutical Association [2017-YY-02-11].