Pattern Recognition in Pharmacokinetic Data Analysis

被引:0
作者
Johan Gabrielsson
Bernd Meibohm
Daniel Weiner
机构
[1] Division of Pharmacology and Toxicology,Department of Biomedical Sciences and Veterinary Public Health, SLU
[2] University of Tennessee Health Science Center,College of Pharmacy
来源
The AAPS Journal | 2016年 / 18卷
关键词
absorption; area under the curve; bi-exponential; half-life; induction; intravenous and extravascular dosing; lag time; mono-exponential; multi-compartment; nonlinear elimination; plasma concentration-time courses; target-mediated drug disposition; transporters;
D O I
暂无
中图分类号
学科分类号
摘要
Pattern recognition is a key element in pharmacokinetic data analyses when first selecting a model to be regressed to data. We call this process going from data to insight and it is an important aspect of exploratory data analysis (EDA). But there are very few formal ways or strategies that scientists typically use when the experiment has been done and data collected. This report deals with identifying the properties of a kinetic model by dissecting the pattern that concentration-time data reveal. Pattern recognition is a pivotal activity when modeling kinetic data, because a rigorous strategy is essential for dissecting the determinants behind concentration-time courses. First, we extend a commonly used relationship for calculation of the number of potential model parameters by simultaneously utilizing all concentration-time courses. Then, a set of points to consider are proposed that specifically addresses exploratory data analyses, number of phases in the concentration-time course, baseline behavior, time delays, peak shifts with increasing doses, flip-flop phenomena, saturation, and other potential nonlinearities that an experienced eye catches in the data. Finally, we set up a series of equations related to the patterns. In other words, we look at what causes the shapes that make up the concentration-time course and propose a strategy to construct a model. By practicing pattern recognition, one can significantly improve the quality and timeliness of data analysis and model building. A consequence of this is a better understanding of the complete concentration-time profile.
引用
收藏
页码:47 / 63
页数:16
相关论文
共 29 条
[1]  
Duan JZ(2010)Drug-drug interaction pattern recognition Drugs R D 10 9-24
[2]  
Cobelli C(1980)Parameters and structural identifiability concepts and ambiguities: a critical review and analysis Am J Physiol 239 R7-24
[3]  
DiStefano JJ(2000)Within-and between-subject variations in pharmacokinetic parameters of ethanol by analysis of breath, venous blood and urine Br J Clin Pharmacol 49 399-408
[4]  
Norberg Å(2003)Role of variability in ethanol kinetics—review Clin Pharmacokinet 42 1-31
[5]  
Gabrielsson J(2012)Dynamics of target-mediated drug disposition: characteristic profiles and parameter identification J Pharmacokinet Pharmacodyn 39 429-451
[6]  
Jones AW(2012)Immunogenicity to therapeutic proteins: impact on PK/PD and efficacy AAPS J 14 296-302
[7]  
Hahn RG(1998)Time course of enzyme induction in humans: effect of pentobarbital on nortriptyline metabolism Clin Pharmacol Ther 64 18-26
[8]  
Norberg Å(1974)Pharmacokinetic evaluation of anticonvulsants prior to efficacy testing exemplified by carbamazepine in epileptic monkey model Epilepsia 15 351-59
[9]  
Jones AW(2007)Misuse of the wellstirred model of hepatic drug clearance Drug Metab Dispos 35 501-502
[10]  
Hahn RG(undefined)undefined undefined undefined undefined-undefined