Stereoselective Pharmacokinetics of Chlorpheniramine and the Effect of Ranitidine

Abstract

This single-dose, randomized, crossover study was carried out to investigate the potential effect of ranitidine on the pharmacokinetics of chlorpheniramine. The study also afforded an opportunity to add to the limited data currently available on the stereoselective pharmacokinetics of chlorpheniramine. Healthy subjects received a single oral 4 mg dose of racemic chlorpheniramine on two separate occasions: alone, and on day 6 of dosing with ranitidine 75 mg b.i.d. for 8 days. Serum concentrations and urinary recovery of (S)-(+)- and (R)-(-)-chlorpheniramine were unaffected by administration of ranitidine, indicating no pharmacokinetic drug-drug interaction. The observed chlorpheniramine pharmacokinetic data were consistent with previous data and indicated approximately 2.5-fold higher serum concentrations of the (S)-(+) enantiomer. Previously reported high variability in chlorpheniramine pharmacokinetics was greatly reduced by well-controlled food and fluid intake.

Evaluation of enantioselective binding of basic drugs to plasma by ACE

“…For each pair of enantiomers, the bound concentration of the first eluted enantiomer (E 1 ) was lower than the second enantiomer (E 2 ), indicating that E 2 has greater affinity towards proteins than its antipode which is also observed in the protein binding percentage values estimated for each enantiomer. The results obtained for chlorpheniramine and bupivacaine agree with the ones published in bibliography [11,12] since the (S)-(1)-enantiomer of both compounds exhibits higher affinity towards plasma proteins than its antipode.…”

“…Few data are known about the stereoselective binding of these compounds to whole plasma. A previous study about chlorpheniramine enantiomers showed that the pharmacologic activity of this compound resides primarily in the (S)-(1)-enantiomer, which exhibits higher plasma concentrations and a longer half-life than the (R)-(2)-enantiomer [11]. As regards bupivacaine, studies in vivo with animals have concluded that the (R)-isomer is more cardiotoxic than the (S)-isomer [12].…”

Halogenation effects of pheniramines on the complexation with β-cyclodextrin

“…However, pharmacological activity of such compounds is attributed primarily to their S-enantiomers, which have been reported to exhibit higher plasma concentrations and a longer half-life than the R-enantiomers. S-enantiomers are approximately 100 times more potent than the R-enantiomers, while R-enantiomers are largely responsible for the sedative side effects of these drugs [4][5][6]. Thus, methods of separation to obtain singleenantiomer forms to improve the efficacy of the drug or suppress the side effects associated with the other enantiomer must be developed [1,7].…”

Enantioselective determination of chlorpheniramine in various formulations by HPLC using carboxymethyl-β-cyclodextrin as a chiral additive

“…The receptor binding studies in a variety of tissues showed that the d-isomer (d-CP) is approximately 100 times more potent than the l-isomer (l-CP) (Tran et al, 1978;Chang et al, 1979). Though the clinical activity of CP is mainly associated with the d-enantiomer (Koch et al, 1998), it is mostly marketed as a racemic mixture of d-CP and l-CP. Only a few preparations are available as a single enantiomer (d-CP).…”