ASPECTS OF THEOPHYLLINE CLEARANCE IN CHILDREN

Michaelis-Menten pharmacokinetic parameters for theophylline were esti mated in a three-month infant following an accidental overdose of intr avenous aminophylline. Fitting of time-concentration data was performe d rising nonlinear regression with MKMODEL, A mixed order elimination model was superior to a first order model. Parameter estimates were st andardized to a 70 kg human using an allometric power model. Parameter estimates (SE) were: maximum rate of metabolism (Vmax) 71 (42) mg.h(- 1), Michaelis-Menten constant (Km) 32.3 (33.5) mg.l(-1), volume of dis tribution (Vd) 46.9 (2.6) l. This Michaelis-Menten constant is lower t han that reported for adults and consequently non-linear elimination w ill occur at lower plasma concentrations in infants than in adults. Th eophylline clearance has traditionally been reported as directly propo rtional to body weight, This per kilogram model gives an erroneous imp ression that clearance is greatest in early childhood and then decreas es with age until adult rates are reached in late adolescence. Age-rel ated clearance values reported in the literature were reviewed using a n allometric 3/4 power model, This size model demonstrates that cleara nce increases in infancy and reaches adult rates in the first one to t wo years of life.