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Review
. 2021 May 23;26(11):3113.
doi: 10.3390/molecules26113113.

Enantioselectivity in Drug Pharmacokinetics and Toxicity: Pharmacological Relevance and Analytical Methods

Maria Miguel Coelho  1 , Carla Fernandes  1   2 , Fernando Remião  3 , Maria Elizabeth Tiritan  1   2   4
Affiliations
Review

Enantioselectivity in Drug Pharmacokinetics and Toxicity: Pharmacological Relevance and Analytical Methods

Maria Miguel Coelho et al. Molecules. .

Abstract

Enzymes, receptors, and other binding molecules in biological processes can recognize enantiomers as different molecular entities, due to their different dissociation constants, leading to diverse responses in biological processes. Enantioselectivity can be observed in drugs pharmacodynamics and in pharmacokinetic (absorption, distribution, metabolism, and excretion), especially in metabolic profile and in toxicity mechanisms. The stereoisomers of a drug can undergo to different metabolic pathways due to different enzyme systems, resulting in different types and/or number of metabolites. The configuration of enantiomers can cause unexpected effects, related to changes as unidirectional or bidirectional inversion that can occur during pharmacokinetic processes. The choice of models for pharmacokinetic studies as well as the subsequent data interpretation must also be aware of genetic factors (such as polymorphic metabolic enzymes), sex, patient age, hepatic diseases, and drug interactions. Therefore, the pharmacokinetics and toxicity of a racemate or an enantiomerically pure drug are not equal and need to be studied. Enantioselective analytical methods are crucial to monitor pharmacokinetic events and for acquisition of accurate data to better understand the role of the stereochemistry in pharmacokinetics and toxicity. The complexity of merging the best enantioseparation conditions with the selected sample matrix and the intended goal of the analysis is a challenge task. The data gathered in this review intend to reinforce the importance of the enantioselectivity in pharmacokinetic processes and reunite innovative enantioselective analytical methods applied in pharmacokinetic studies. An assorted variety of methods are herein briefly discussed.

Keywords: chiral analyses; chiral stationary phases; chirality; enantiomers; metabolism.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Types of stereoselective metabolism.
Figure 2
Figure 2
Omeprazole enantiomers metabolism.
Figure 3
Figure 3
Phenytoin metabolism.
Figure 4
Figure 4
Methadone metabolism. EDDP = 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine; EMDP = 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline.
Figure 5
Figure 5
Venlafaxine metabolism.
Figure 6
Figure 6
Nicotine metabolism.
See this image and copyright information in PMC

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