Interaction of beta-blockers with the renal uptake transporter OCT2.

Aim: The uptake of drugs from the blood into the renal tubular cells is a key determinant for renal secretion and may influence their systemic plasma concentrations and extrarenal effects. Metformin, used for treatment of type 2 diabetes, is taken up into renal tubular cells by the organic cation transporter 2 (OCT2). Because many patients with type 2 diabetes receiving metformin are concomitantly treated with beta-blockers, we tested whether beta-blockers can inhibit OCT2-mediated drug transport.

Interaction of oral antidiabetic drugs with hepatic uptake transporters: focus on organic anion transporting polypeptides and organic cation transporter 1.

Objective: The uptake of drugs into hepatocytes is a key determinant for hepatic metabolism, intrahepatic action, their subsequent systemic plasma concentrations, and extrahepatic actions. In vitro and in vivo studies indicate that many drugs used for treatment of cardiovascular diseases (e.g.

The association of ABCB1 polymorphisms and elevated serum digitoxin concentrations in geriatric patients.

Objective: Digitoxin is a known substrate of the efflux pump P-glycoprotein (gene name: ABCB1). P-glycoprotein expression was shown to be modulated by single nucleotide polymorphisms in the ABCB1 gene, but it remains unclear whether these polymorphisms influence digitoxin blood levels. Our objective was to examine the association of ABCB1 C3435T genotype and elevated serum digitoxin concentrations (SDC) in a cohort of 77 geriatric patients consecutively admitted to a geriatric department over a 12-month period.

Role of p-glycoprotein inhibition for drug interactions: evidence from in vitro and pharmacoepidemiological studies.

Objectives: We determined in vitro the potency of macrolides as P-glycoprotein inhibitors and tested in hospitalised patients whether coadministration of P-glycoprotein inhibitors leads to increased serum concentrations of the P-glycoprotein substrates digoxin and digitoxin.

Methods: In vitro, the effect of macrolides on polarised P-glycoprotein-mediated digoxin transport was investigated in Caco-2 cells. In a pharmacoepidemiological study, we analysed the serum digoxin and digitoxin concentrations with and without coadministration of P-glycoprotein inhibitors in hospitalised patients.

Impact of the CYP3A5 genotype on midazolam pharmacokinetics and pharmacodynamics during intensive care sedation.

Objective: Information is lacking on whether the CYP3A5 genotype affects the disposition and effects of midazolam during the long-term intensive care sedation of patients. This study was undertaken to estimate whether the CYP3A5 genotype can explain a relevant portion of pharmacokinetic interindividual variability.

Methods: We determined the CYP3A5 genotype in 71 Caucasian patients who underwent long-term sedation during intensive care treatment.