Drug interaction studies with repaglinide: Repaglinide on digoxin or theophylline pharmacokinetics and cimetidine on repaglinide pharmacokinetics

Drug interaction studies were carried out to ensure that hypoglycemia due t o inhibition of repaglinide elimination or chronic hyperglycemia due to inh ibition of repaglinide absorption was avoided. Conversely, the effects of r epaglinide on the pharmacokinetics of drugs with only a narrow margin betwe en effective and toxic concentrations, such as digoxin or theophylline, wer e determined. The studies reported here compared monotherapy with combined therapies in healthy volunteers. There were no significant differences betw een the pharmacokinetic parameters of repaglinide when given as monotherapy and when administered concurrently with cimetidine. Similarly, the coadmin istration of repaglinide and digoxin did not influence the pharmacokinetics of digoxin administered alone. When repaglinide was coadministered with th eophylline, the only pharmacokinetic change was that the peak plasma theoph ylline concentration was slightly reduced. No direct drug-drug interactions were found in these studies, suggesting that repaglinide may be coprescrib ed with cimetidine, digoxin, or theophylline at the dosage used for monothe rapy. Journal of Clinical Pharmacology, 2000;40:184-192 (C)2000 the America n College of Clinical Pharmacology.