European Journal of Clinical Pharmacology

, Volume 22, Issue 4, pp 359–365

Pharmacokinetics of chlorpheniramine after intravenous and oral administration in normal adults

  • S. M. Huang
  • N. K. Athanikar
  • K. Sridhar
  • Y. C. Huang
  • W. L. Chiou


Plasma and urinary levels of chlorpheniramine (CPM) and its 2 demethylated metabolites were measured by HPLC after i.v. and oral dosing. In 5 mg (maleate) i.v. bolus studies in 2 subjects, plasma CPM levels were fitted to triexponential equations with terminal half-lives (t1/2) of 23 and 22 h and area of 3.6 and 3.21/kg, respectively. Intravenous data predicted hepatic blood extraction ratios for the 2 subjects to be 0.06 and 0.07, respectively. Absolute bioavailability from oral solution (10 mg) was 59 and 34%, and from tablets (8 mg) 44 and 25%, respectively, indicating extensive gut first-pass metabolism. Mean t1/2 from 7 oral fasting studies in 5 subjects was 28 h (19–43 h). Mean absorption lag time was 0.7 h (0.4–1.3 h), and mean peak time was 2.8 h (2–4 h). In 2 subjects, 6 mg solutions were given every 12 h for 9 doses; good correlation between single and multiple dose kinetics was found. Significant accumulation was demonstrated in simulation studies with frequent daily dosing. Estimated accumulation ratios vary from 4.1 to 9.4 (mean 6.5). The t1/2 from urinary data (collected for 12 days) was consistent with plasma data. The above results suggest the need to reexamine the current practice of frequent daily dosing and the use of sustained or controlled release dosage forms of this drug. The possible cause of reduced plasma clearance of CPM in renal patients is discussed.

Key words

chlorpheniramine pharmacokinetics oral absorption half-life bioavailability volume of distribution 


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Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • S. M. Huang
    • 1
  • N. K. Athanikar
    • 1
  • K. Sridhar
    • 2
  • Y. C. Huang
    • 1
  • W. L. Chiou
    • 1
  1. 1.Department of Pharmacy, College of PharmacyUniversity of Illinois, Medical CenterChicagoUSA
  2. 2.Cook County HospitalChicagoUSA

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