Stereoselective pharmacokinetics of chlorpheniramine and the effect of ranitidine.
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.
Clinical Pharmacology, Glaxo Wellcome Inc., 5 Moore Drive, Research Triangle Park, North Carolina 27709, USA. kmk9284@glaxowellcome.com
K M
KM
Koch
R L
RL
O'Connor-Semmes
I M
IM
Davis
Y
Y
Yin
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002744:Chlorpheniramine / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D006207:Half-Life; D006634:Histamine H1 Antagonists / Q000493:pharmacokinetics*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D011899:Ranitidine / Q000494:pharmacology*; D013237:Stereoisomerism
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D002744:Chlorpheniramine; D011899:Ranitidine