Role of the magnesium cation on antihypertensive molecule-human serum albumin binding: affinity chromatography approach.
The role of the Mg2+ cation on antihypertensive molecule binding on human serum albumin (HSA) was studied by affinity chromatography. The thermodynamic data corresponding to this binding were determined for a wide range of Mg2+ concentrations (c). For the nifedipine molecule, an increase in the Mg2+ concentration produced a decrease in binding due to a decrease in the electrostatic interactions. For verapamil and diltiazem, which have the highest solvent accessible surface area, the solute binding on HSA was divided into two Mg2+ concentration regions. For a low c value below c(c) (approximately 1.6 mmol/l), the binding dependence with c was similar to that of nifedipine. For c above c(c) the hydrophobic effect created in the bulk solvent associated with a decrease in the van der Waals interactions between the solute molecule and the HSA implied a decrease in its binding. These results showed that for patients with hypertension, an Mg2+ supplementation during treatment with these antihypertensive molecules can increase the active pharmacological molecule concentration.
Guillaum
Y C
YC
Laboratoire de Chimie Analytique, Faculté de Médecine et de Pharmacie, Place Saint Jacques, Besançon, France. yves.guillaume@univ-fcomte.fr
Nicod
L
L
Truong-Thanh
T
T
Guinchard
C
C
Robert
J F
JF
Thomassin
M
M
D000959:Antihypertensive Agents / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D002413:Cations, Divalent; D002846:Chromatography, Affinity / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D008274:Magnesium / Q000502:physiology*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D055672:Static Electricity
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D002413:Cations, Divalent; D012709:Serum Albumin; D008274:Magnesium