Effect of age and sex on theophylline clearance in young subjects

The joint effects of age and gender on theophylline plasma clearance (Cl(p)) were assessed using an analysis of covariance technique. Data from several literature sources and from our laboratory were collated for this analysis with only nonsmoking subjects aged 1.3 to 30.0 years considered. The values of Cl(p) exhibited markedly greater variability in the younger subjects, necessitating development of a weighted linear least-squares program to fit the data. The data exhibited a linear decrease in Cl(p) with increasing age regardless of sex. A gender influence was evident over the age range of 4 to 20 years. Male Cl(p) values tended to be higher than those of females over this age interval [25.5 ml/hr/kg higher (31%) at 4 years and 12.5 ml/hr/kg higher (22%) at 20 years]. These differences are statistically significant, and since they represent a divergence of greater than 20%, may be clinically significant as well. The statistical technique employed may be of value in future pharmacokinetic studies for the examination of multiple effects on pharmacokinetic parameters.