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  • Title: Theophylline. Pooled Michaelis-Menten parameters (Vmax and Km) and implications.
    Author: Wagner JG.
    Journal: Clin Pharmacokinet; 1985; 10(5):432-42. PubMed ID: 3899457.
    Abstract:
    The literature on theophylline is confusing since in the same dose range one article will report linear kinetics while another will report non-linear kinetics. Single dose clearances and lower steady-state clearances of theophylline, recently reported in the literature, were used to estimate pooled Vmax and Km values of the Michaelis-Menten equation for 10 normal subjects. The mean Vmax was 1960 mg/day and the mean Km was 24.1 mg/L. These values were then utilised to: explain another set of different oral clearances following doses of 2 and 6 mg/kg reported in the literature; estimate relative effects of dose rate and type of input on absolute bioavailability; estimate AUC (0-infinity) as a function of single dose over the range 0 to 1500 mg; estimate the average steady-state serum concentration of theophylline (Cssav and steady-state oral clearance (CLsspo) as a function of dose rate in mg/day; illustrate how Michaelis-Menten kinetics alters the apparent first-order elimination rate constant and the half-life estimated from terminal log-linear plots at concentrations appreciably lower than the Km value; and illustrate how Michaelis-Menten kinetics affects the estimation of a zero-order absorption rate constant using the Wagner-Nelson method.
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