Abstract
The pharmacokinetics and metabolism of 3H-chlorpheniramine maleate have been studied in man. After a p.o. dose (12 mg), 3H appeared rapidly in plasma and at two hours was equivalent to 32.48 mµg of chlorpheniramine per ml; radioactivity persisted in plasma through 48 hours. At five minutes after an i.v. dose (4 mg), 3H in plasma was equivalent to 20.88 mµg of drug per ml and 3H again persisted in plasma. This persistence of plasma 3H was most probably due to tissue deposition of 3H-drug (or metabolites), directly indicated by its large volume of distribution, 250% of body weight. The drug was 72% bound to plasma protein. Unchanged drug as well as its metabolites were present in plasma, however, and in contrast to the persistent levels of 3H in plasma, the levels of 3H-chlorpheniramine declined steadily, although slowly, after the i.v. dose and after the two-hour peak after administration p.o. The plasma half-life of a p.o. dose was 12 to 15 hours and that of an i.v. dose, 28 hours. Excretion of the 3H-drug was slow and only one-third of a p.o. or i.v. dose was recovered from the excreta during 48 hours after administration. The p.o. dose was completely absorbed, however, and only small amounts of the 3H-drug were excreted into feces after its administration. Fecal excretion of 3H of an i.v. dose indicated that 3H-chlorpheniramine underwent an enterohepatic circulation. Chlorpheniramine was extensively metabolized and excreted in the urine as mono- and didesmethyl chlorpheniramine, two unidentified metabolites and small amounts of chlorpheniramine. The greatest portion of the drug was excreted as an unidentified polar metabolite(s).
Footnotes
- Received May 13, 1971.
- Accepted October 21, 1971.
- © 1972 by The Williams & Wilkins Co.
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