digoxin and isobutylparaben

Pharmaceutical excipients have been shown to influence drug disposition through modulating transport protein.. This study assessed the effect of single dose administration of parabens on the pharmacokinetics (PK) of digoxin, a probe substrate of p-glycoprotein (p-gp), in vivo. Also, the effect of multiple dosing of parabens on p-gp expression was examined.. Rats were randomized into four groups that received either the vehicle, 25 mg/ kg verapamil, 100 mg/ kg isobutyl paraben, or 100 mg/ kg 2-ethyl hexyl paraben, which was followed by giving 0.2 mg/ kg digoxin via oral gavage. Blood samples were collected at different time points, digoxin concentration was measured using LC/MS-MS, and digoxin PK parameters were estimated. Another set of rats received multiple doses of parabens for 14 days, followed by measuring intestinal and hepatic mRNA expression of p-gp using qRT-PCR.. Single dose administration of verapamil significantly increased C. The lack of isobutylparaben and 2-ethylhexyl paraben effect on p-gp may suggest the insignificant interaction of parabens with p-gp drug substrates, which could be considered for safety when designing pharmaceutical formulations.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Digoxin; Parabens; Pharmaceutical Preparations; Rats; RNA, Messenger; Verapamil