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Experience with Nonmem: Analysis of Routine Phenytoin Clinical Pharmacokinetic Data

 

作者: SheinerLewis B.,   GraselaThaddeus H.,  

 

期刊: Drug Metabolism Reviews  (Taylor Available online 1984)
卷期: Volume 15, issue 1-2  

页码: 293-303

 

ISSN:0360-2532

 

年代: 1984

 

DOI:10.3109/03602538409015067

 

出版商: Taylor&Francis

 

数据来源: Taylor

 

摘要:

AbstractNONMEM, a program package the produces the extended least squares estimates of population parameters for a nonlinear mixed-effect model, has been applied to two data sets from patients routinely receiving phenytoin. A general model for the data is proposed. The models used in previous, standard-method analyses of each data set are compared to the general model using NONMEM. The comparison involves two questions: The first asks whether the parameters estimated previously agree with NONMEM estimates when the original model is used. We find that for fixed-effect parameters they generally do, while for interindividual random-effect parameters the previous methods' estimates appear upward biased relative to NONMEM. Second, the original model per se is compared to the general model by comparing the best fit to each. The general model is clearly superior. NONMEM's ability to distinguish among models, and to precisely estimate their parameters from sparse individual data, is illustrated and verified.

 

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