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A Model for Dosing Gentamicin in Children and Adolescents that Adjusts for Tissue Accumulation with Continuous Dosing1

 

作者: William E. Evans,   R. Huntley Taylor,   Sandor Feldman,   William R. Crom,   Gaston Rivera,   Gary C. Yee,  

 

期刊: Clinical Pharmacokinetics  (ADIS Available online 1980)
卷期: Volume 5, issue 3  

页码: 295-306

 

ISSN:0312-5963

 

年代: 1980

 

出版商: ADIS

 

数据来源: ADIS

 

摘要:

The pharmacokinetics of gentamicin were evaluated in 50 children and adolescents during a multiple dose course of therapy. Parameters of a 2-compartment pharmacokinetic model were derived from serial serum concentrations and urinary excretion rates measured for up to 11 days following the last dose of gentamicin administered to 10 of these patients. These parameters were used to simulate changes in serum concentrations and half-lives that would occur during a standard 6-hour dosing interval with continuous dosing.The data indicated that the half-life for decline in serum concentrations after the first dose was 76 ± 8% of the half-life at steady-state, and that the half-life after the fourth dose exceeded 90% of the steady-state half-life. These underestimations of the steady-state serum half-life were incorporated into a 1-compartment model to simulate steady-state peak and nadir serum concentrations by using pharmacokinetic parameters measured after the first dose of gentamicin administered to 40 patients. Steady-state serum concentrations predicted by the true 1-compartment model and by the adjusted model were compared with concentrations measured at steady-state. The concentrations predicted by the former model were significantly different from and consistently less than measured concentrations. Concentrations predicted by the adjusted model were not significantly different from concentrations measured at steady-state.These data indicate that the new model offers a simple and more accurate method of simulating steady-state concentrations from pharmacokinetic parameters measured after initial doses of gentamicin and offers an improved model for individualising therapy.

 

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