Document Detail


Pharmacokinetic-pharmacodynamic modelling of insulin: comparison of indirect pharmacodynamic response with effect-compartment link models.
MedLine Citation:
PMID:  12078995     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The pharmacokinetic and pharmacodynamic modelling of insulin has been reported using a combined pharmacokinetic/pharmacodynamic (PK/PD) model, in which a hypothetical effect compartment is linked to a pharmacokinetic compartment. Review of the literature, however, indicated that the recently developed PK/PD models have consisted of an indirect pharmacodynamic response component, but none of them has been applied to the modelling of insulin. To study the relative relevance of the indirect pharmacodynamic response model and the effect-compartment link model in modelling the pharmacokinetics and pharmacodynamics of insulin, regular human insulin was administered intravenously at a dose of 0.1 IU kg(-1) to healthy Yucatan minipigs (after an overnight fasting). The plasma concentrations of insulin were measured by radioimmunoassay at predetermined time intervals, while blood glucose levels were monitored continuously using a glucose monitor. Analysis of the plasma insulin and the blood glucose profiles was performed by fitting with various PK/PD models and the results indicated that all of the 12 sets of plasma insulin data (after normalizing by the basal levels) have been adequately fitted to the two-compartment open pharmacokinetic model (a mean+/-s.e. correlation coefficient of 0.996+/-0.001 was obtained). The mean+/-s.e. correlation coefficient, the weighted residuals sum of squares (WRSS), and the Akaike's information criterion (AIC) were found, respectively, to be 0.935+/-0.008, 624+/-67, and 522+/-9 for the inhibitory indirect pharmacodynamic response model and 0.941+/-0.010, 547+/-63 and 513+/-9 for the stimulatory indirect pharmacodynamic response model, as compared with 0.725+/-0.041, 2309+/-276 and 628+/-10 for the effect-compartment link model. Based on these results, one may conclude that the indirect pharmacodynamic response model is a more appropriate approach for modelling the PK/PD of insulin than the effect-compartment link model.
Authors:
Senshang Lin; Yie W Chien
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  The Journal of pharmacy and pharmacology     Volume:  54     ISSN:  0022-3573     ISO Abbreviation:  J. Pharm. Pharmacol.     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-06-24     Completed Date:  2003-02-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376363     Medline TA:  J Pharm Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  791-800     Citation Subset:  IM    
Affiliation:
St John's University, College of Pharmacy and Allied Health Professions, Jamaica, NY 11439, USA. linse@stjohns.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Glucose / metabolism
Humans
Hypoglycemic Agents / blood,  pharmacokinetics*,  pharmacology*
Injections, Intravenous
Insulin / blood,  pharmacokinetics*,  pharmacology*
Male
Models, Biological
Radioimmunoassay
Swine, Miniature
Time Factors
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Hypoglycemic Agents; 11061-68-0/Insulin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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