The disposition of chlorpheniramine was examined in seven children, 6-14 years of age, following a O.l-mg/kg iv dose. Postinjection serum chlorpheniramine levels in each subject declined biexponentially, with the greatest intersubject variability occurring in the initial distribution of the drug. The volume of distribution at steady state ranged from 1.20 to 5.46 liters/kg. The chlorpheniramine serum clearance varied approximately twofold (234-470 ml/hr/kg) and generally decreased with age. The chlorpheniramine elimination half-life in children (mean of 9.6 hr) appeared shorter than that in adults, probably due to higher chlorpheniramine serum clearance in children.
Keyphrases Chlorpheniramine maleate-pharmacokinetics of intravenous drug in children Pharmacokinetics-intravenous chlorpheniramine maleate in children Antihistaminics-pharmacokinetics of intravenous chlorpheniramine maleate in children Antihistamines represent a primary pharmacological approach to therapy for conditions such as allergic rhinitis and urticaria in patients of all ages. An appropriate antihistamine and its dose are often chosen by trial and error, sometimes with marginal success. Failure of an antihistamine to provide adequate relief could be due to intrinsic limitations in the drug's effectiveness or to suboptimal dosing due to a lack of pharmacokinetic information.
Although chlorpheniramine maleate has been a widely used antihistamine for many years, only limited pharmacokinetic information on it has been reported, and no information for children is available. Studies with adults reveal inconsistencies in biological half-life, with values ranging from 2 to 43 hr. (Table I) (1-7). Recently reported longer half-lives for chlorphreniramine have been attributed to longer blood sampling periods (6).
A highly sensitive assay procedure for chlorpheniramine was recently developed (8). The distribution and elimination of chlorpheniramine following intravenous administration of the drug to children were examined using this technique. This report presents the results of these studies.
EXPERIMENTAL Methods-Seven children, 6-14 years of age and 24-63 kg (Table 11), were studied. The children were participating in a study of chronic rhinitis, and all had perennial rhinitis but no other significant medical problems. None had received antihistamines or any other medication for at least 1 month prior to the study. The children were studied for a 24-hr period'.
Chlorpheniramine maleate2, 0.10 mg/kg, was administered intravenously over 5 min by an infusion pump3. Serum was obtained from venous blood samples collected immediately prior to drug administration and at 0.25,0.5, 1,2,4,6,8,12, and 24 hr following completion of the 5-min infusion. Serum was stored at -70' until analyzed.
Chlorpheniramine analysis was performed by GLC-mass spectrometry. A tetradeuterated analog was prepared for use as the internal standard. Each serum sample (2.0 ml) was mixed with 85 ng of the internal stan-