Quiral Inversion of Ibuprofen after an Oral Administration Under Complete Fasting and Fed Conditions in Caucasian Healthy Subjects

Background: The aim was to determine the effect of feeding on chiral inversion of Ibuprofen isomers. Method: Six healthy volunteers participated in a two-treatment crossover study where a single dose of Ibuprofen racemate was given. One stage consisted in an 8-hour interval of fasting, while in the other, the drug was administered with a solution of saccharose and a standard food intake regimen was implemented.

Recent advances in chiral analysis for biosamples in clinical research and forensic toxicology

This article covers current methods and applications in chiral analysis from 2010 to 2020 for biosamples in clinical research and forensic toxicology. Sample preparation for aqueous and solid biological samples prior to instrumental analysis were discussed in the article. GC, HPLC, capillary electrophoresis and sub/supercritical fluid chromatography provide the efficient tools for chiral drug analysis coupled to fluorescence, UV and MS detectors. The application of chiral analysis is discussed in the article, which involves differentiation between clinical use and drug abuse, pharmacokinetic studies, pharmacology/toxicology evaluations and chiral inversion. Typical chiral analytes, including amphetamines and their analogs, anesthetics, psychotropic drugs, β-blockers and some other chiral compounds, are also reviewed.

Stereoselective Pharmacokinetics and Chiral Inversions of Some Chiral Hydroxy Group Drugs

Background: Chiral safety, especially chiral drug inversion in vivo, is the top priority of current scientific research. Medicine researchers and pharmacists often ignore that one enantiomer will be converted or partially converted to another enantiomer when it is ingested in vivo. So that, in the context that more than 50% of the listed drugs are chiral drugs, it is necessary and important to pay attention to the inversion of chiral drugs. Methods: The metabolic and stereoselective pharmacokinetic characteristics of seven chiral drugs with one chiral center in the hydroxy group were reviewed in vivo and in vitro including the possible chiral inversion of each drug enantiomer. These seven drugs include (S)-Mandelic acid, RS-8359, Tramadol, Venlafaxine, Carvedilol, Fluoxetine and Metoprolol. Results: The differences in stereoselective pharmacokinetics could be found for all the seven chiral drugs, since R and S isomers often exhibit different PK and PD properties. However, not every drug has shown the properties of one direction or two direction chiral inversion. For chiral hydroxyl group drugs, the redox enzyme system may be one of the key factors for chiral inversion in vivo. Conclusion: In vitro and in vivo chiral inversion is a very complex problem and may occur during every process of ADME. Nowadays, research on chiral metabolism in the liver has the most attention, while neglecting the chiral transformation of other processes. Our review may provide the basis for the drug R&D and the safety of drugs in clinical therapy.