Pharmacokinetic behaviour of R-(+)- and S-(-)-amlodipine after single enantiomer administration

Journal of Chromatography. B, Biomedical Sciences and Applications
J LuksaS Milutinovic

Abstract

Amlodipine, 3-ethyl 5-methyl-2-[(2-aminoethoxymethyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methy l-3,5-pyridinedicarboxylate, is a chiral calcium antagonist, currently on the market and in therapeutic use as a racemate. The pharmacokinetic behaviour of R-(+)- and S-(-)-amlodipine after single enantiomer administration to healthy male human volunteers together with comparative administration of the racemic mixture of both enantiomers were studied. Plasma levels were studied as a function of time and assayed using an enantioselective chromatographic method (coupled chiral and achiral HPLC) with on-line solid-phase extraction and UV absorbance detection. The method was validated separately for the R-(+)- and S-(-)-enantiomer, respectively. Results of the study indicate that the pharmacokinetic behaviour of R-(+)- and S-(-)-amlodipine after single enantiomer administration is comparable to that of each enantiomer after administration of the racemate. No racemization occurs in vivo in human plasma after single enantiomer administration.

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Citations

Jan 25, 2003·Journal of Biochemical and Biophysical Methods·Nobuo Inotsume, Masahiro Nakano
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Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maria Miguel CoelhoMaria Elizabeth Tiritan
Mar 9, 2011·The Journal of Organic Chemistry·Tobias Harschneck, Stefan F Kirsch

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