STEREOSELECTIVE PHARMACOKINETICS OF CHLORPHENIRAMINE AND THE EFFECT OF RANITIDINE

This single-dose, randomized, crossover study was carried out to inves tigate the potential effect of ranitidine on the pharmacokinetics of c hlorpheniramine. The study also afforded an opportunity to add to the limited data currently available on the stereoselective pharmacokineti cs of chlorpheniramine. Healthy subjects received a single oral 4 mg d ose 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 conc entrations and urinary recovery of (S)-(+)- and (R)-(-)-chlorphenirami ne were unaffected by administration of ranitidine, indicating no phar macokinetic drug-drug interaction. The observed chlorpheniramine pharm acokinetic data were consistent with previous data and indicated appro ximately 2.5-fold higher serum concentrations of the (S)-(+) enantiome r. Previously reported high variability in chlorpheniramine pharmacoki netics was greatly reduced by well-controlled food and fluid intake.