We evaluated the significance of the interaction between rifampin and verapamil in six volunteers who received single doses of verapamil, 10 mg intravenously (IV), then 120 mg orally two days later. Subjects were then given rifampin, 600 mg orally every day for 15 days. After 13 and 15 days of rifampin therapy, the IV and oral doses of verapamil were repeated. Electrocardiograms (ECG) were done...

OBJECTIVE The primary objective of this study was to investigate the interaction potential of carmegliptin with P-glycoprotein transporter in vitro and in vivo. A secondary objective was to investigate the safety and tolerability of carmegliptin alone or co-administered with verapamil. RESEARCH DESIGN AND METHODS The inhibition potential of carmegliptin was tested in vitro and in a non-random...

A stereospecific capillary zone electrophoresis (CZE) method was developed for the determination of verapamil (VER) and its main metabolite norverapamil (NOR) in human plasma. Optimal temperature, cyclodextrin selectors (CDs), pH of background electrolyte (BGE) and voltage were established to obtain complete separation of the chiral analytes and clopidogrel internal standard (I.S.) during one a...

In this acute study a pig jejunal intestinal perfusion model with multiple plasma sampling sites and three different administration routes was used to investigate the quantitative contribution of the intestine versus liver to the first-pass extraction of each enantiomer of verapamil (VER). A subclinical dose of ketoconazole (8 mg) was coadministered in the perfusion solution to selectively inhi...

Some mechanism-based inhibitors cause irreversible inhibition by forming a metabolic intermediate complex (MIC) with cytochrome P450. In the present study, 54 molecules (substrates of CYP3A and amine-containing compounds that are not known substrates of CYP3A) were spectrophotometrically assessed for their propensity to cause MIC formation with recombinant CYP3A4 (+b(5)). Comparisons of common ...

Positron emission tomography (PET) imaging of P-glycoprotein (P-gp) in the blood-brain barrier can be important in neurological diseases where P-gp is affected, such as Alzheimer´s disease. Radiotracers used in the imaging studies are present at very small, nanomolar, concentration, whereas in vitro assays where these tracers are characterized, are usually performed at micromolar concentration,...

Verapamil (VP) is used as a racemate but shows stereoselective pharmacokinetics and pharmacodynamics. It undergoes extensive first-pass metabolism. Stereoselective first-pass metabolism in the intestine and liver was investigated in vivo and in vitro to determine its impact on the disposition of VP and its main metabolite, norverapamil (NVP). VP racemate was administered to rats i.v., p.o., and...