Coadministration of glyburide and minoxidil, drugs with opposing effects on potassium channels.
BACKGROUND
Adenosine triphosphate (ATP)-sensitive potassium (K+) channels are modulated by drugs, so that they are opened by vasodilators such as minoxidil but are closed by hypoglycemic agents such as glyburide (glibenclamide). Animal studies and in vitro evidence suggests that the coadministration of drugs with opposing effects on K+ channels attenuates their pharmacodynamic effects.


METHODS
To investigate whether this important pharmacodynamic interaction occurs in humans, we administered 5 mg minoxidil, 2.5 mg glyburide or both in a double-blind fashion to nine healthy subjects. Glucose and insulin responses during an intravenous glucose tolerance test (0.3 gm/kg) were measured and blood pressure was recorded for 8 hours. In an additional four subjects the effect of 5 mg glyburide on the hypotensive effect of 5 mg minoxidil was examined.


RESULTS
None of the parameters of glucose metabolism differed significantly when subjects received glyburide alone, minoxidil alone, or glyburide with minoxidil. Minoxidil or minoxidil in combination with 2.5 mg glyburide resulted in a similar significant decrease in blood pressure compared with the response to glyburide alone. The hypotensive effect of minoxidil was smaller in the four subjects who received the higher dose of glyburide, but significant hypoglycemia (blood glucose concentration < 60 mg/dl) occurred in three of the four subjects.


CONCLUSIONS
We conclude that, in healthy volunteers, the coadministration of 2.5 mg glyburide and 5 mg minoxidil does not result in attenuation of the blood pressure-lowering effect of minoxidil. The smaller hypotensive response in four subjects who received 5 mg glyburide and 5 mg minoxidil suggests the possibility of a dose-related drug interaction. Studies with strict clamping of blood glucose concentrations will be required to address this possibility.
Stein
C M
CM
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA.
Brown
N
N
Carlson
M G
MG
Campbell
P
P
Wood
A J
AJ
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004336:Drug Antagonism; D005951:Glucose Tolerance Test; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male; D008914:Minoxidil / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D015221:Potassium Channels / Q000187:drug effects*; D012016:Reference Values; D012083:Renin / Q000097:blood
D000959:Antihypertensive Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D015221:Potassium Channels; D008914:Minoxidil; D012083:Renin; D005905:Glyburide; D009638:Norepinephrine