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Theophylline Pooled Michaelis-Menten Parameters (Vmaxand Km) and Implications

 

作者: John G. Wagner,  

 

期刊: Clinical Pharmacokinetics  (ADIS Available online 1985)
卷期: Volume 10, issue 5  

页码: 432-442

 

ISSN:0312-5963

 

年代: 1985

 

出版商: ADIS

 

数据来源: ADIS

 

摘要:

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 Vmaxand Km values of the Michaelis-Menten equation for 10 normal subjects. The mean Vmaxwas 1960 mg/day and the mean Km was 24.1 mg/L. These values were then utilised to: (1) explain another set of different oral clearances following doses of 2 and 6 mg/kg reported in the literature; (2) estimate relative effects of dose rate and type of input on absolute bioavailability; (3) estimate AUC (0-∞) as a function of single dose over the range 0 to 1500mg; (4) estimate the average steady-state serum concentration of theophylline (Cssavand steady-state oral clearance (CLsspo) as a function of dose rate in mg/day; (5) 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 (6) illustrate how Michaelis-Menten kinetics affects the estimation of a zero-order absorption rate constant using the Wagner-Nelson method.

 

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