The renal clearance of theophylline was determined in 12 experiments with six healthy human adult volunteers and was found to decrease from 8.50+/-2.20 to 276.+/-1.13 ml/min/m2 during 8 hours after oral administration of a single dose of theophylline, 200 mg/m2. There was a strong and highly statistically significant positive correlation between the renal clearance of theophylline and the urine flow rate for each subject, but there was no consistent correlation between renal clearance and plasma concentrations of theophylline.
The pharmacokinetics of theophylline following intravenous injection of aminophylline, 4 mg/kg of body weight, were determined in 30 children with asthma and in 6 normal adult volunteers. The average total clearance of theophylline was 87 ml/hr/kg in the children and 57 ml/hr/kg in the adults. The biologic half-life of theophylline in the children ranged from 1.42 to 7.85 hours, reflecting mainly pronounced interindividual differences in the elimination rate constant of the drug. There was no significant difference between the children and adults with respect to the distribution rate constants and apparent volumes of distribution of theophylline, but the elimination rate constant of the drug was considerably higher in children than in adults. Thus, children eliminate theophylline more rapidly on the average than do adults and also show pronounced interindividual differences in the elimination of the drug. Compared to adults, children tend to require relatively larger amounts of theophylline per day and the doses may have to be given at shorter intervals of time.
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