Top 1 Biorxiv Papers Today in Pharmacology And Toxicology


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#1. Unexpected differences in the pharmacokinetics of N-acetyl DL-leucine enantiomers after oral dosing and their clinical relevance
Grant C Churchill, Michael Strupp, Antony Galione, Frances M Platt
These results suggest that during chronic administration of the racemate, the D-enantiomer would accumulate, which could have negative effects. The enantiomers of many chiral drugs not only exhibit different pharmacological effects in regard to targets that dictate therapeutic and toxic effects, but are also handled differently in the body due to pharmacokinetic effects. We investigated the pharmacokinetics of the enantiomers of N-acetyl-leucine after administration of the racemate (N-acetyl-DL-leucine) or purified, pharmacologically active L-enantiomer (N-acetyl-L-leucine). Compounds were administered orally to mice. Plasma and tissue samples were collected at predetermined time points (0.25 to 8 h), quantified with liquid chromatography/mass spectrometry, and pharmacokinetic constants were calculated using a noncompartmental model. When administered as the racemate, both the maximum plasma concentration (Cmax) and the area under the plasma drug concentration over time curve (AUC) were much greater for the D-enantiomer relative...
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