Acetyl tributyl citrate (ATBC) is an (the Food and Drug Administration) FDA-approved substance for use as a pharmaceutical excipient. It is used in pharmaceutical coating of solid oral dosage forms such as coated tablets or capsules. However, the information of ATBC on its pharmacokinetics is limited. The aim of this study is to investigate the pharmacokinetic properties of ATBC using liquid chromatography–tandem mass spectrometric (LC–MS/MS) analysis. ATBC was rapidly absorbed and eliminated and the bioavailability was 27.4% in rats. The results of metabolic stability tests revealed that metabolic clearance may have accounted for a considerable portion of the total clearance of ATBC. These pharmacokinetic data would be useful in studies investigating the safety and toxicity of ATBC.

Acetyl triethyl citrate (ATEC) is a water-soluble plasticizer used in pharmaceutical plasticized polymers. In this study, the pharmacokinetics and metabolism of ATEC were investigated using liquid chromatography–tandem mass spectrometry (LC–MS/MS) in rats. Plasma protein precipitation with methanol was used for sample preparation. For chromatographic separation, a C18 column was used. The mobile phases consisted of 0.1% formic acid and 90% acetonitrile, and gradient elution was used. The following precursor-product ion pairs were selected for reaction monitoring analysis: 319.1 m/z → 157 m/z for ATEC and 361.2 m/z → 185.1 m/z for tributyl citrate (internal standard) in positive ion mode. The LC–MS/MS method was fully validated and successfully applied to a pharmacokinetic study of ATEC in rats. The pharmacokinetic study showed that the volume of distribution and mean residence time of ATEC were higher after oral administration than after intravenous administration, pointing to extensive first-pass metabolism and distribution in tissue. In addition, the plasma concentration profile of the postulated metabolites of ATEC was investigated in plasma, urine, and feces. The resulting data indicated that ATEC was extensively metabolized and excreted mainly as metabolites rather than as the parent form. The developed analytical method and the data on the pharmacokinetics and metabolism of ATEC may be useful for understanding the safety and toxicity of ATEC.

Cytochalasans are a group of structurally diverse fungal polyketide-amino acid hybrid metabolites that exhibit diverse biological functions. Asperchalasine A was identified and isolated from an extract of the marine-derived fungus, Aspergillus. Asperchalasine A is a cytochalasan dimer which consists of two cytochalasan molecules connected by an epicoccine. This study investigated the potential antiangiogenic effects of Aspergillus extract and asperchalasine A, which significantly inhibited cell adhesion and tube formation in human umbilical vein endothelial cells (HUVECs). Aspergillus extract and asperchalasine A decreased the vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR)-2 mRNA expression in a concentration-dependent manner. In addition, Aspergillus extract and asperchalasine A inhibited angiogenesis via downregulation of VEGF, p-p38, p-extracellular signal-regulated protein kinase (ERK), p-VEGFR-2, and p-Akt signaling pathways. Moreover, Aspergillus extract and asperchalasine A significantly inhibited the amount of blood vessel formation in fertilized chicken eggs using a chorioallantoic membrane assay. Our results provide experimental evidence of this novel biological activity of the potential antiangiogenic substances, Aspergillus extract, and asperchalasine A. This study also suggests that Aspergillus extract and its active component asperchalasine A are excellent candidates as adjuvant therapeutic substances for cancer prevention and treatment.

HSG4112, a racemic drug, is a new anti-obesity agent. In this study, the stereoselective pharmacokinetics of HSG4112 were investigated in rats and dogs, and the underlying mechanism was investigated. The plasma concentrations of HSG4112(S) and HSG4112(R) were quantitated in plasma from rats and beagle dogs after IV and/or oral administration of racemic HSG4112. The concentration of HSG4112(S) was significantly higher than that of HSG4112(R) in rat plasma. Contrarily, the concentration of HSG4112(R) was significantly higher than HSG4112(S) in dog plasma. A metabolic stability test with liver microsomes showed that HSG4112(S) was more stable than HSG4112(R) in rat liver microsomes, but the difference between stereoisomers did not appear in dog liver microsomes. However, the stereoselectivity was observed in dog liver and intestinal microsomes after uridine 5’-diphospho-glucuronic acid was added. Thus, stereoselective metabolism by uridine 5’-diphospho-glucuronosyltransferases is mainly responsible for the stereoselective pharmacokinetics in dogs. These results suggest that the species difference in the stereoselective plasma pharmacokinetics of HSG4112 is due to the stereoselective metabolism.