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Published on: May 2, 2017
Effect of fluconazole on the pharmacokinetics and pharmacodynamics of nateglinide
Mikko Niemi1, Mikko Neuvonen, Laura Juntti-Patinen
1Department of Clinical Pharmacology, University of helsinki and Helsinki University Central Hospital, Finland. mikko.niemi@helsinki.fi
Objective:
Our aim was to investigate the possible effects of fluconazole on the pharmacokinetics and pharmacodynamics of nateglinide, a new short-acting meglitinide analog antidiabetic drug.
Methods:
In a randomized, double-blind, crossover study with 2 phases, 10 healthy volunteers took 200 mg fluconazole (400 mg on day 1) or placebo once daily for 4 days. On day 4, they ingested a single 30-mg dose of nateglinide. Plasma nateglinide and blood glucose concentrations were measured for up to 7 hours.
Results:
Fluconazole raised the total area under the plasma concentration-time curve from time 0 to infinity of nateglinide by 48% (range, 20%-73%; P <.00001) and prolonged its half-life from 1.6 to 1.9 hours (P <.05), but the peak plasma nateglinide concentration remained unchanged. The peak plasma concentration of the M7 metabolite of nateglinide was reduced by 34% by fluconazole (P <.001), and its half-life was prolonged from 2.2 to 3.5 hours (P <.05). No significant differences were seen in the blood glucose response to nateglinide between the phases.
Conclusions:
Fluconazole raised the plasma concentrations and reduced the systemic elimination of nateglinide probably by inhibiting its cytochrome P4502C9-mediated biotransformation. Concomitant use of fluconazole with nateglinide may prolong its blood glucose-lowering effect.
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