Urinary excretion of chlorpheniramine and its metabolites in children.

The pharmacokinetics and urinary excretion of chlorpheniramine were studied in 11 patients, aged 6-16 years, with allergic rhinitis. In these children, chlorpheniramine had a mean elimination half-life of 13.1 +/- 6.6 h, a mean clearance rate of 7.23 +/- 3.16 mL/min/kg, and a mean apparent volume of distribution of 7.0 +/- 2.8 L/kg. Over 48 h, the recovery in urine was as follows: chlorpheniramine, 11.3 +/- 6.7%; demethylchlorpheniramine , 23.3 +/- 11.1%; and didemethylchlorpheniramine , 9.6 +/- 9.4%. Urine flow rate and urine pH were uncontrolled and ranged from 2.2 to 113.3 mL/h and 5.1-7.9, respectively, over the 48-h period. In some children urine flow rate and pH were constant, while in others there was great variability. When drug and metabolite excretion rates versus both urine flow rates and pH values were analyzed by multiple linear regression, the results were significantly better (p less than or equal to 0.05) than when each factor was analyzed independently. The excretion rate of chlorpheniramine and its two demethylated metabolites decreased as urine pH increased and urine flow rate decreased. This information must be considered in future pharmacokinetic studies of this drug.

Sustained-release theophylline for treatment of asthma in preschool children.

Theo-Dur, a sustained-release theophylline formulation, was administered every 12 hours for three months to ten asthmatic children aged 3 to 7 years, with no evidence of adverse reaction or tolerance. There was significant temporal variation in serum theophylline concentrations. The mean difference between the peak and trough concentrations was 6.5 micrograms/mL (range, 3 to 14 micrograms/mL) in a 12-hour period. Serum theophylline concentrations correlated well with pulmonary function test results. Nine or more hours after a Theo-Dur dose, some children needed additional bronchodilator treatment and had impairment of pulmonary function. We recommend that children aged 7 years or younger who are given Theo-Dur have monitoring of predose serum theophylline concentrations, symptoms, and signs, as many will require a dose frequency greater than every 12 hours.

Pharmacokinetics and efficacy of chlorpheniramine in children.

Chlorpheniramine is widely used, but there is very little information about its pharmacokinetics and efficacy in children. In 11 patients with allergic rhinitis, ages 6 to 16 yr, we found a mean serum chlorpheniramine half-life of 13.1 +/- 6.3 hr, a mean volume of distribution of 7.0 +/- 2.8 L/kg, and a mean clearance rate of 7.2 +/- 3.2 ml/min/kg. Suppression of symptoms and signs of allergic rhinitis and suppression of the histamine-induced wheal and flare responses occurred when mean serum chlorpheniramine concentration ranged from 2.3 to 12.1 and 4.1 to 10.0 ng/ml, respectively. This combined with the large volume of distribution for the drug, suggest that tissue binding is an important aspect of chlorpheniramine pharmacokinetics.

Ketotifen: a new drug for prophylaxis of asthma in children.

Ketotifen, an orally active, prophylactic anti-asthmatic drug, was compared with placebo in a double-blind, three-month parallel-group trial in 20 children. Children receiving ketotifen were more likely to reduce concomitant medications and had significant improvement over time in asthma scores and mean flows at 75%, 50%, and 25% of vital capacity. They also had a significantly increased incidence of dry mouth and significant weight gain compared to those receiving placebo. In some children with asthma, ketotifen may be a useful alternative to existing drugs.

The pharmacokinetics of theophylline in an infant with hepatic failure.

In a 6 1/2-month-old infant with hepatic failure secondary to hereditary tyrosinemia, the theophylline clearance rate of 0.016 liter/kg/h was reduced for age and the serum half-life was prolonged to 18.0 h. Theophylline, 3.4 micrograms/ml, and caffeine, 2.2 micrograms/ml, were identified in a urine sample obtained 48 h after the test dose of theophylline, but no 1-methyluric acid, 1,3-dimethyluric acid or 3-methylxanthine were detected. This is the first infant with liver dysfunction and impaired theophylline disposition to be reported.