Effects of induction and inhibition of Cytochrome P-450 enzymes on the pharmacokinetics and pharmacodynamics of oral antidiabetic drugs
Year: 2001
Type: dissertation
Abstract: The interactions of rifampicin with the sulfonylureas glibenclamide, glimepiride, and glipizide are probably mainly explained by induction of CYP2C9 by rifampicin.Induction of the P-glycoprotein by rifampicin probably also contributed to the interaction between rifampicin and glibenclamide.The susceptibilities of these antidiabetic drugs to interaction with rifampicin differ significantly, and glipizide seems to be least susceptible to a clinically significant interaction with rifampicin.Rifampicin had the greatest effect on the CYP3A4 substrate repaglinide, indicating that repaglinide is susceptible to clinically significant interactions resulting in loss of blood glucose control with rifampicin and other potent inducers of CYP3A4.CYP2C9 inhibitors can raise plasma concentrations of glimepiride, and the concomitant use of fluconazole or other potent inhibitors of CYP2C9 with glimepiride may markedly increase the risk of hypoglycemia.Clarithromycin raised the plasma concentrations and the effects of repaglinide probably by inhibiting its CYP3A4-mediated metabolism.The concomitant use of potent inhibitors of CYP3A4 with repaglinide may enhance its blood glucose-lowering effect and increase the risk of hypoglycemia.
Source: Työväentutkimus Vuosikirja
Author: Mikko Niemi
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: green
Funder: Helsingin Yliopisto
OpenAlex ID: W1566888489