Stereoselective interaction of tolvaptan with amiodarone under racemic metabolic impact by CYP3A5 genotypes in heart failure patients.

Purpose: The diuretic effect of tolvaptan is largely blood level-dependent although it does exhibit interindividual differences according to cytochrome P450 (CYP) 3A5 genotype. This study aimed to investigate the pharmacokinetic relationship between plasma tolvaptan and its monohydroxylate enantiomers and the factors affecting their metabolism in heart failure patients.

Methods: Japanese heart failure patients (n = 88) receiving oral tolvaptan (median dosage 7.

Case series of elderly patients with scabies topically applied with ivermectin via whole-body bathing.

As a novel method of ivermectin (IVM) administration for the treatment of scabies, we devised a whole-body bathing (WBB), in which patients are immersed in a fluid that contains IVM. A multi-institutional trial for elderly patients with scabies was conducted to investigate the efficacy and safety of IVM-WBB. Seven elderly patients with scabies were enrolled and received IVM-WBB up to four times at 1-week interval.

Simple LC-MS/MS method using core-shell ODS microparticles for the simultaneous quantitation of edoxaban and its major metabolites in human plasma.

Edoxaban is mainly enzymatically converted to a 4-carboxylic acid form (4CA-EDX) and an N-desmethyl form (ND-EDX) in humans. This study aimed to establish a simple liquid chromatography-tandem mass spectrometry method using core-shell octadecyl silica (ODS) microparticles for the simultaneous quantitation of edoxaban and its two major metabolites in human plasma. Analytes extracted from plasma specimens by a one-step deproteinization were separated using a 2.

An enantiomeric quantitative LC-MS/MS method for tolvaptan and its monohydroxylates in human plasma using a reversed-phase separation procedure.

Racemic tolvaptan possessing an asymmetric carbon is metabolized to three pairs of monohydroxylate enantiomers of diol form with V receptor antagonistic activity via CYP3A. This study aimed to develop a simultaneous quantitative liquid chromatography-tandem mass spectrometry method for 5R- and 5S-tolvaptan and their monohydroxylate enantiomers in human plasma and to apply it to patient samples. Deproteinized plasma specimens were separated using a polysaccharide derivative chiral column in a reversed-phase elution mode.

Impact of CYP3A5 genotype on tolvaptan pharmacokinetics and their relationships with endogenous markers of CYP3A activity and serum sodium level in heart failure patients.

Tolvaptan efficacy for heart failure has a large interindividual variation. This study aimed to evaluate the influence of CYP3A5 and ABCB1 genotypes on tolvaptan pharmacokinetics and their relationships with plasma markers of CYP3A activity and laboratory test values in heart failure patients. Fifty-eight heart failure patients receiving oral tolvaptan for volume overload were enrolled.