Fluconazole Increases Plasma
Concentrations of Nateglinide
Clinicians should be aware of the possibility
of increased blood glucose-lowering efficacy of
nateglinide if fluconazole and nateglinide are
combined.
Fluconazole potently inhibits cytochrome P450
(CYP) 2C9, the authors explain, and in vitro studies
suggest that CYP2C9, as well as CYP3A4, participates
in the biotransformation of nateglinide.
Dr. Niemi and colleagues from University of Helsinki,
Finland, studied the single-dose pharmacokinetics
of nateglinide with or without fluconazole administration
(400 mg on day 1 and 200 mg on days 2-4) in 10
healthy volunteers.
Fluconazole increased the area under the time-concentration
curve (AUC) of nateglinide by 48% and prolonged
its half-life from 1.6 to 1.9 hours, the authors
report.
The maximum concentration of nateglinide's principal
metabolite fell by 34%, the report indicates,
but the metabolite's half-life increased from
2.2 to 3.5 hours. Nateglinide's maximum plasma
concentration did not change significantly.
Blood glucose levels were not significantly different
with and without the administration of fluconazole,
the researchers note.
In previous studies, the same fluconazole treatment
resulted in a 138% increase in the AUC of the
sulfonylurea glimepiride, the investigators write,
and a 100-mg daily dose of fluconazole significantly
increased the AUC of glipizide (49%) and glyburide
(44%).
Dr. Niemi commented that, "It is possible
(I would not yet say probable, because of lack
of data from patients with type 2 diabetes mellitus)
that nateglinide is a safer hypoglycemic drug
than glimepiride (and possibly other sulfonylureas)
if fluconazole therapy is required." Clin
Pharmacol Ther 2003;74:25-31.
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Did YOU KNOW:
Metformin Reduces Inflammation: Common diabetes
drug lowers risk by inhibiting proinflammatory
factor. University at Buffalo (UB) endocrinologists
have shown for the first time that the concentration
of a proinflammatory compound known as MIF is
increased in the blood plasma of the obese, and
that metformin, a standard medicine prescribed
for diabetes, suppresses its formation. Presented
at the 85th annual meeting of the Endocrine Society
held recently in Philadelphia and at the preceding
American Diabetes Association meeting in New Orleans.
