Modeling and simulation of the effect of proton pump inhibitors on magnesium homeostasis. 1. Oral absorption of magnesium.
Mol Pharm
; 9(12): 3495-505, 2012 Dec 03.
Article
em En
| MEDLINE
| ID: mdl-23051182
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Simulação por Computador
/
Omeprazol
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Inibidores da Bomba de Prótons
/
Absorção Intestinal
/
Magnésio
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Deficiência de Magnésio
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article