1H nuclear magnetic resonance and clinical studies of interaction of calcium antagonists and hypoglycemic sulfonylureas.
The hypoglycemic effect of gliclazide is mainly due to its action on ATP stimulated K+ channels, but the calcium ionophoretic effect of this drug may also be involved in its physiological properties. Using 1H NMR we demonstrated the antiionophoretic effect of nifedipine and diltiazem. We attempted to verify whether this in vitro interaction also occurs in vivo. A clinical trial, was performed on patients treated concomitantly with gliclazide and nifedipine or diltiazem. Results showed that no in vivo interaction occurred. The discrepancy between in vivo and in vitro results may be explained by a too weak plasma concentration in the case of nifedipine and by a large plasma protein binding in the case of diltiazem.
Monges
A M
AM
Laboratoire de Biophysique, Faculté de Pharmacie, Marseille, France.
Pisano
P
P
Aujoulat
P
P
Salducci
D
D
Durand
A
A
Panagides
D
D
Bory
M
M
Crevat
A
A
D000255:Adenosine Triphosphate; D000368:Aged; D001665:Binding Sites; D001786:Blood Glucose / Q000032:analysis; D000001:Calcimycin / Q000737:chemistry / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D004110:Diltiazem / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005907:Gliclazide / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects
D001786:Blood Glucose; D007328:Insulin; D015221:Potassium Channels; D000001:Calcimycin; D000255:Adenosine Triphosphate; D004110:Diltiazem; D005907:Gliclazide; D009543:Nifedipine; D002118:Calcium