title: Pharmacokinetic behaviour of R-(+)- and S-(-)-amlodipine after single enantiomer administration.
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.
authors.affiliation: Lek Pharmaceutical and Chemical Company d.d., Ljubljana, Slovenia.
authors.forename: J
authors.initials: J
authors.lastname: Luksa
authors.forename: D
authors.initials: D
authors.lastname: Josic
authors.forename: M
authors.initials: M
authors.lastname: Kremser
authors.forename: Z
authors.initials: Z
authors.lastname: Kopitar
authors.forename: S
authors.initials: S
authors.lastname: Milutinovic
mesh_terms: D000284:Administration, Oral; D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D016014:Linear Models; D008297:Male; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D017311:Amlodipine