The cytochrome P4503A4 inhibitor clarithromycin increases the plasma concentrations and effects of repaglinide.

Article Details

Citation

Niemi M, Neuvonen PJ, Kivisto KT

The cytochrome P4503A4 inhibitor clarithromycin increases the plasma concentrations and effects of repaglinide.

Clin Pharmacol Ther. 2001 Jul;70(1):58-65. doi: 10.1067/mcp.2001.116511.

PubMed ID
11452245 [ View in PubMed
]
Abstract

OBJECTIVE: Our objective was to study the effects of the macrolide antibiotic clarithromycin on the pharmacokinetics and pharmacodynamics of repaglinide, a novel short-acting antidiabetic drug. METHODS: In a randomized, double-blind, 2-phase crossover study, 9 healthy volunteers were treated for 4 days with 250 mg oral clarithromycin or placebo twice daily. On day 5 they received a single dose of 250 mg clarithromycin or placebo, and 1 hour later a single dose of 0.25 mg repaglinide was given orally. Plasma repaglinide, serum insulin, and blood glucose concentrations were measured up to 7 hours. RESULTS: Clarithromycin increased the mean total area under the concentration-time curve of repaglinide by 40% (P <.0001) and the peak plasma concentration by 67% (P <.005) compared with placebo. The mean elimination half-life of repaglinide was prolonged from 1.4 to 1.7 hours (P <.05) by clarithromycin. Clarithromycin increased the mean incremental area under the concentration-time curve from 0 to 3 hours of serum insulin by 51% (P <.05) and the maximum increase in the serum insulin concentration by 61% (P <.01) compared with placebo. No statistically significant differences were found in the blood glucose concentrations between the placebo and clarithromycin phases. CONCLUSIONS: Even low doses of the cytochrome P4503A4 (CYP3A4) inhibitor clarithromycin increase the plasma concentrations and effects of repaglinide. Concomitant use of clarithromycin or other potent inhibitors of CYP3A4 with repaglinide may enhance its blood glucose-lowering effect and increase the risk of hypoglycemia.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
ClarithromycinCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Details
Drug Interactions
DrugsInteraction
Repaglinide
Erythromycin
The serum concentration of Repaglinide can be increased when it is combined with Erythromycin.
Repaglinide
Sirolimus
The serum concentration of Repaglinide can be increased when it is combined with Sirolimus.
Repaglinide
Dirithromycin
The serum concentration of Repaglinide can be increased when it is combined with Dirithromycin.
Repaglinide
Telithromycin
The serum concentration of Repaglinide can be increased when it is combined with Telithromycin.
Repaglinide
Candicidin
The serum concentration of Repaglinide can be increased when it is combined with Candicidin.