heme metabolites biliverdin IXβ and IXδ are integral to lifestyle adaptations associated with chronic infection.

Unlabelled: is a versatile opportunistic pathogen requiring iron for its survival and virulence within the host. The ability to switch to heme as an iron source and away from siderophore uptake provides an advantage in chronic infection. We have recently shown the extracellular heme metabolites biliverdin IXβ (BVIXβ) and BVIXδ positively regulate the heme-dependent cell surface signaling cascade.

Validation of a method for itraconazole and major metabolite hydroxyitraconazole for LC-MS/MS analysis with application in a formulation clinical study.

A high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the analysis of itraconazole (ITZ) and hydroxyitraconazole (ITZ-OH) as part of a human pharmacokinetic study of novel tablet formulations. We demonstrated that 100 µL of plasma sample can be used with a protein precipitation extraction by optimizing different composition of acid in organic solvent for the precipitation solvent, giving comparable recovery to more time-consuming liquid-liquid or solid phase extractions. Additionally, we have shown that by monitoring the halogen isotopic peak for ITZ as well as optimizing chromatographic conditions, we are able to avoid carryover and endogenous interferences, allowing for a lower limit of quantification for our study.

Differential effects of metformin-mediated BSEP repression on pravastatin and bile acid pharmacokinetics in humans: A randomized controlled trial.

Metformin has been shown to repress transcription of the bile salt export pump (BSEP) in human primary hepatocytes. The primary objective of this study was to assess the effect of oral metformin on the human pharmacokinetics (PKs) of two BSEP probe substrates: pravastatin and chenodeoxycholic acid (CDCA; also known as chenodiol). Endogenous bile acid levels were assessed as a secondary measure of metformin impact.

Lack of an Effect of Polysorbate 80 on Intestinal Drug Permeability in Humans.

Purpose: Despite no broad, direct evidence in humans, there is a potential concern that surfactants alter active or passive drug intestinal permeation to modulate oral drug absorption. The purpose of this study was to investigate the impact of the surfactant polysorbate 80 on active and passive intestinal drug absorption in humans.

Methods: The human (n = 12) pharmacokinetics (PK) of three probe substrates of intestinal absorption, valacyclovir, chenodeoxycholic acid (CDCA), and enalaprilat, were assessed.