The Effect of Famotidine on the Metabolism of Metoprolol Tartrate in Human Liver Microsomes

Ran XU; Enfu FENG; Yuyu XIONG; Jiade ZHU; Gonghao HE

doi:10.12259/j.issn.2095-610X.S20250203

Volume 46 Issue 2

Feb. 2025

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Ran XU, Enfu FENG, Yuyu XIONG, Jiade ZHU, Gonghao HE. The Effect of Famotidine on the Metabolism of Metoprolol Tartrate in Human Liver Microsomes[J]. Journal of Kunming Medical University, 2025, 46(2): 17-22. doi: 10.12259/j.issn.2095-610X.S20250203

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Ran XU, Enfu FENG, Yuyu XIONG, Jiade ZHU, Gonghao HE. The Effect of Famotidine on the Metabolism of Metoprolol Tartrate in Human Liver Microsomes[J]. Journal of Kunming Medical University, 2025, 46(2): 17-22. doi: 10.12259/j.issn.2095-610X.S20250203

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The Effect of Famotidine on the Metabolism of Metoprolol Tartrate in Human Liver Microsomes

doi: 10.12259/j.issn.2095-610X.S20250203

Department of Clinical Pharmacy，920th Hospital of Joint Logistics Support Force of People’s Liberation Army，Kunming Yunan 650032，China

Received Date: 2024-09-18
Available Online: 2025-01-05
Publish Date: 2025-02-18

Abstract

Abstract

Objective To explore the enzymatic reaction kinetics of metoprolol tartrate in an in vitro human liver microsome incubation experiment and to explore the effect of famotidine on the metabolism of metoprolol tartrate. Methods An LC-MS/MS method was developed to accurately measure the concentration of metoprolol tartrate in a human liver microsomal incubation system. A human liver microsome incubation system was established to determine the optimal incubation time and protein concentration; using the substrate depletion method, the enzymatic reaction kinetics parameters of metoprolol tartrate （such as V_max and K_m）. Series concentrations of famotidine were co-incubated with metoprolol tartrate, and the concentration of metoprolol tartrate was measured to evaluate the effect of famotidine on its metabolism. Results The optimal incubation time for metoprolol tartrate in human liver microsomes was found to be 60 minutes, with an optimal protein concentration of 1.0 mg/mL. The enzymatic reaction kinetics parameters were V_max = 0.07 µmol/min/mg protein and K_m = 7.84 µmol/L. Conclusion The results indicated that famotidine did not produce a significant inhibitory effect on the metabolism of metoprolol tartrate in human liver microsome incubation system, suggesting that the combination of these two drugs may be relatively safe.
- Metoprolol tartrate,
- Famotidine,
- Human liver microsomes,
- LC-MS/MS,
- Kinetics of enzymatic reactions

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