Office of Generic Drugs, Office of Pharmaceutical Science, §Office of Pharmacovigilance and Epidemiology, Office of Surveillance and Epidemiology, and †Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation, Food and Drug Administration , Rockville, Maryland, United States.
Mol Pharm. 2012 Dec 3;9(12):3495-505. doi: 10.1021/mp300323q. Epub 2012 Nov 2.
Prolonged use of proton pump inhibitors has reportedly caused rare clinically symptomatic hypomagnesemia. A review of the literature suggests PPI drugs may impair intestinal magnesium absorption. With the goal of preventing PPI-induced hypomagnesemia, an oral absorption-centric model was developed by referencing literature data. Our modeling with human data reveals that magnesium absorption is substantial in the distal intestine. We then perform simulations by referring to the reported reduction in mid to distal intestinal pH caused by one week of oral esomeprazole, and to reported reduction of the divalent cation-sensitive current when the carboxyl side chains of glutamic and aspartic residues in the binding channels of TRPM6/TRPM7 were neutralized. Our simulations reveal that short-term PPI therapy may cause a very small reduction (5%) in the serum magnesium level, which is qualitatively consistent with the reported 1% reduction in magnesium absorption following 1 week of omeprazole in humans. Simulations provide insight into the benefit of frequent but small dose of magnesium supplementation in maintaining the serum magnesium level when magnesium deficiency occurs.
据报道，质子泵抑制剂的长期使用会导致罕见的有临床症状的低镁血症。文献综述表明，PPI 药物可能会损害肠道镁的吸收。为了预防 PPI 引起的低镁血症，我们参考文献数据，建立了一个以口服吸收为中心的模型。我们用人体数据进行建模，结果表明镁在远端肠道有大量吸收。然后，我们参考报告中口服埃索美拉唑一周引起的中到远端肠道 pH 值的降低，以及报告中当 TRPM6/TRPM7 结合通道中谷氨酸和天冬氨酸残基的羧基侧链被中和时，二价阳离子敏感电流降低的情况，进行模拟。我们的模拟结果表明，短期 PPI 治疗可能会导致血清镁水平非常小的降低（5%），这与在人体中使用奥美拉唑 1 周后镁吸收减少 1%的报告结果定性一致。模拟结果为当发生镁缺乏时，频繁但小剂量补充镁以维持血清镁水平提供了一些见解。
