Abstract：
:This study was designed to investigate the pharmacokinetics/pharmacodynamics (PK/PD) risk factors preceding the onset of type 2 diabetes using a population-based Bayesian nonlinear hierarchical model to describe the glucose-insulin kinetics. One hundred fifty-two healthy subjects with a family history of type 2 diabetes were recruited. Each subject received an intravenous glucose tolerance test (IVGTT) and the data of glucose and insulin was collected when entering the study. After the test, subjects were followed up to 25 years and further divided into the diabetic outcome group and non-diabetic outcome group according to the follow-up results. A glucose-insulin kinetic model was developed to account for the physiology and molecular biology of the insulin biphasic secretion and glucose-insulin interactions with a minimal structure. The population PK/PD parameters of the two groups were estimated from the proposed glucose-insulin kinetic model. The relationships between the population PK/PD parameters and the diabetic follow-up results were evaluated. A high insulin baseline concentration, a lower maximum insulin-dependent glucose removal and a lower insulin removal rate constant were found associated with the development of type 2 diabetes in the high risk population. The study shows that the very early pre-diabetic pharmacokinetic differences exist and can be helpful for prediction of development of type 2 diabetes.
journal_name
J Pharmacokinet Pharmacodynjournal_title
Journal of pharmacokinetics and pharmacodynamicsauthors
Lin CW,Veng-Pedersen Pdoi
10.1007/s10928-009-9130-zsubject
Has Abstractpub_date
2009-10-01 00:00:00pages
421-41issue
5eissn
1567-567Xissn
1573-8744journal_volume
36pub_type
杂志文章abstract：:HbA1c is the most commonly used biomarker for the adequacy of glycemic management in diabetic patients and a surrogate endpoint for anti-diabetic drug approval. In spite of an empirical description for the relationship between average glucose (AG) and HbA1c concentrations, obtained from the A1c-derived average glucose...
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abstract：AIM:Chemotherapy with indisulam causes myelosuppression. This study aimed to evaluate the influence of patient-related covariates on pharmacokinetics and pharmacodynamics, to identify patients at risk for severe myelosuppression and to develop a dosing algorithm for treatment optimization. METHODS:Pharmacokinetic and ...
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更新日期：2009-02-01 00:00:00
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