PHARMACOKINETIC EVALUATION OF CHLORPHENIRAMINE MALEATE IN MAN AND SEVERAL DOMESTIC ANIMAL SPECIES
Abstract
The pharmacokinetics of chlorpheniramine maleate were evaluated in man and several domestic animal species. Chlorpheniramine serum levels were quantified using a gas chromatographic procedure with nitrogen-phosphorous detection. Chlorpheniramine and the internal standard were isolated from serum utilizing a three step extraction procedure. The method has a minimum sensitivity limit of 1.0 ng/ml and exhibits linearity to 250.0 ng/ml. The reproducibility of the procedure was evidenced by a coefficient of variation of 5.8% for a chlorpheniramine concentration of 2.5 ng/ml and 3.6% at the 50.0 ng/ml level. After intravenous dosing with 0.1 mg/kg, the drug was eliminated rapidly in the equine, swine, ovine, and canine species. The elimination half-lives for these species ranged from 1.3 hours to 2.6 hours in contrast to the longer reported values for man (12 - 30 hours). Chlorpheniramine was found in the breast milk of a lactating mother after a 4.0 mg oral dose. A peak level of 15.0 ng/ml was observed 2.0 hours after dosing. Dexchlorpheniramine, the pharmacologically active isomer of chlorpheniramine, was administered orally to five human subjects. The elimination half-life was found to be similar to reported values for the racemic mixture. Secondary peaks were observed in the concentration-time profiles in four of the subjects who ingested a large, fatty meal 5 hours after dosing, indicating the possibility of a reabsorption process. One subject ate a light, low-fat meal and did not exhibit a secondary peak. The secondary peak phenomenon was further investigated in swine after oral and I.V. dosing with racemic chlorpheniramine. A definite second peak occurred in one of the three swine; however, it was not possible to make a conclusive statement on the existence of a reabsorption process. The systemic bioavailability of chlorpheniramine was very low in this species, with only 2.4 to 22% of an oral dose reaching the systemic circulation.
Degree
Ph.D.
Subject Area
Pharmacology
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