Incidence of apparent Michaelis-Menten kinetic behavior of theophylline and its parameters (Vmax and Km) among asthmatic children and adults.
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.
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*
D003692:Delayed-Action Preparations; D013806:Theophylline