[A liquid chromatographic method for quantifying unbound micafungin in human plasma and the relationship between the concentrations of unbound and total micafungin in plasma].

This report describes a modified method for the quantitative determination of unbound micafungin (MCFG) in human plasma that is unrelated to chemical methods currently in use, and the relationship between the concentration of unbound and total MCFG in plasma of the patients. The mobile phase consisted of 50 mM phosphate buffer:tetrahydrofuran (65:35, v/v). Samples were fractionated on a C-18 column.

The relationship between the plasma concentration of bepridil and its efficacy in the treatment of atrial fibrillation in Japanese patients.

Bepridil hydrochloride is used for treatment of atrial fibrillation (AF) in Japan. We investigated the relationship between plasma concentrations of bepridil just before dosing (Cbep) and its clinical efficacy in Japanese patients (n=36) with AF. Patients were treated orally with 100, 150 or 200 mg/d bepridil.

An LC method for quantifying bepridil in human plasma using 1-naphthol as the internal standard.

A modified method for the quantitative determination of bepridil hydrochloride in human plasma is described. This method is unrelated to chemical methods currently in use. The mobile phase is 50 mM phosphate buffer (pH3.

Efflux transport of N-monodesethylamiodarone by the human intestinal cell-line Caco-2 cells.

Amiodarone (AMD) is a benzofurane derivative with class III antiarrhythmic activity that is effective in controlling intractable cardiac arrhythmias. One of the most common and serious drug interactions in clinical practice is the interaction between digoxin and an antiarrhythmic agent. It has been reported that AMD and N-monodesethylamiodarone (DEA), the active metabolite of AMD, inhibit the P-glycoprotein (P-gp/MDR1)-mediated digoxin transport.

Characterization of intestinal absorption and enterohepatic circulation of mycophenolic Acid and its 7-O-glucuronide in rats.

To assess the mechanism of gastrointestinal disorders by mycophenolate mofetil (MMF), the intestinal absorption and enterohepatic circulation of mycophenolic acid (MPA), an active metabolite of MMF, and its 7-O-glucuronide (MPAG) were investigated using rat intestinal loops and a linked-rat model. The stability of MPAG in the intestinal fluids, the toxicity of MPA and MPAG to intestinal mucosa, and biliary excretion of MPAG in rats with acute renal failure (ARF) were also characterized. MPA was rapidly and extensively absorbed from the rat intestine whereas MPAG was much less absorbable.

Limited interaction between tacrolimus and P-glycoprotein in the rat small intestine.

The significance of intestinal P-glycoprotein (P-gp) in determining the oral bioavailability of tacrolimus has been still controversial. In this study, we reevaluated the interaction of tacrolimus with P-gp in the rat small intestine, by evaluating its absorption from the rat small intestine and its modulating effect on the absorption of known P-gp substrates (digoxin, methylprednisolone, and vinblastine). Intestinal absorption of tacrolimus itself was as extensive as other P-gp modulators such as cyclosporine and verapamil.

Transepithelial transport of telmisartan in caco-2 monolayers.

Telmisartan is the most recently marketed angiotensin II type 1 receptor antagonist. Drug-drug interactions involving transporters can directly affect the therapeutic safety and efficacy of many important drugs. In clinical practice, telmisartan is coadministered with many kinds of drugs.

Cyclosporin A, but not tacrolimus, inhibits the biliary excretion of mycophenolic acid glucuronide possibly mediated by multidrug resistance-associated protein 2 in rats.

The onset of diarrhea after the administration of mycophenolate mofetil (MMF) is possibly associated with the biliary excretion of its metabolite, mycophenolic acid glucuronide (MPAG). This study was undertaken to clarify the mechanism underlying the biliary excretion of MPAG. Intravenously administered mycophenolic acid (MPA, 5 mg/kg) rapidly disappeared from plasma and was efficiently excreted as MPAG in the bile of Wistar (26% of dose) and Sprague-Dawley rats (21% of dose) over 1 h.