title: Incidence of apparent Michaelis-Menten kinetic behavior of theophylline and its parameters (Vmax and Km) among asthmatic children and adults.
abstract: For assessing the clinical impact of nonlinearity in theophylline elimination, we examined the incidence of individuals with an apparent Michaelis-Menten kinetics (percent change in plasma concentration exceeding that in dose by at least 50%) among asthmatic children (n = 122) and adults (n = 50) screened through a two-step chart review. Forty-nine children and 21 adults had the apparent nonlinearity. When compared overall between the two groups, the maximum elimination rate (Vmax) differed significantly (mean +/- SD, 32.2 +/- 11.5 versus 21.8 +/- 6.7 mg/kg/day, p less than 0.001). The Vmax correlated with age (r = -0.459, p less than 0.001). Such a trend as found in Vmax was not observed in Km. Our results imply that a disproportionate relationship between dose and concentration of theophylline appears to be relatively common in asthmatic children and adults; the metabolic capacity in children is greater than in adults, if the nonlinearity could occur; and caution is needed with these certain susceptible individuals when using linear kinetics for the dosage modification of theophylline.
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003692:Delayed-Action Preparations; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D013806:Theophylline / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D003692:Delayed-Action Preparations; D013806:Theophylline