title: Drug interaction studies with repaglinide: repaglinide on digoxin or theophylline pharmacokinetics and cimetidine on repaglinide pharmacokinetics.
abstract: Drug interaction studies were carried out to ensure that hypoglycemia due to inhibition of repaglinide elimination or chronic hyperglycemia due to inhibition of repaglinide absorption was avoided. Conversely, the effects of repaglinide on the pharmacokinetics of drugs with only a narrow margin between effective and toxic concentrations, such as digoxin or theophylline, were determined. The studies reported here compared monotherapy with combined therapies in healthy volunteers. There were no significant differences between the pharmacokinetic parameters of repaglinide when given as monotherapy and when administered concurrently with cimetidine. Similarly, the coadministration of repaglinide and digoxin did not influence the pharmacokinetics of digoxin administered alone. When repaglinide was coadministered with theophylline, the only pharmacokinetic change was that the peak plasma theophylline concentration was slightly reduced. No direct drug-drug interactions were found in these studies, suggesting that repaglinide may be coprescribed with cimetidine, digoxin, or theophylline at the dosage used for monotherapy.
authors.affiliation: Novo Nordisk A/S, Bagsvaerd, Denmark.
authors.forename: V
authors.initials: V
authors.lastname: Hatorp
authors.forename: M S
authors.initials: MS
authors.lastname: Thomsen
mesh_terms: D000293:Adolescent; D000328:Adult; D002219:Carbamates / Q000493:pharmacokinetics / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology*; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004077:Digoxin / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000502:physiology; D010880:Piperidines / Q000493:pharmacokinetics / Q000494:pharmacology*; D013806:Theophylline / Q000493:pharmacokinetics*
chemical_list: D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; C072379:repaglinide; D004077:Digoxin; D002927:Cimetidine; D003577:Cytochrome P-450 Enzyme System; D013806:Theophylline; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A