Document Detail

Turnover modeling of non-esterified Fatty acids in rats after multiple intravenous infusions of nicotinic Acid.
MedLine Citation:
PMID:  19809543     Owner:  NLM     Status:  In-Data-Review    
The objective of this investigation was to use a pharmacokinetic (PK)/pharmacodynamic (PD) approach to describe and evaluate a PK model of nicotinic acid (NiAc) in guinea pigs and a PD feedback model of changes in non-esterified fatty acid (NEFA) concentrations in rats following multiple intravenous infusions of NiAc at different rates and durations of inhouse and literature (NEFA after extravascular NiAc dosing) data. Serial arterial blood samples were taken for evaluation of NiAc exposure in guinea pigs and NEFA in rats. The biophase kinetics of NiAc was assumed to impact on NEFA turnover with feedback incorporated via an inhibitory moderator compartment. The response acted linearly on the production of moderator, which then acted inversely on the turnover rate of response. The potency, expressed as the amount of NiAc in the biophase causing a 50 % inhibitory effect (ID(50)), was 6.5 nmol +/- 31 % and the half-life of response (t(1/2, kout)) 2 min +/- 18 %. The half-life of tolerance (t(1/2, ktol)) was 9 min +/- 27 %. The model can be used to provide information about factors that determine the time course of NEFA response following different rates and routes of administration of NiAc or NiAc analogues.
Christine Isaksson; Johan Gabrielsson; Kristina Wallenius; Lambertus A Peletier; Helena Toreson
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Publication Detail:
Type:  Journal Article     Date:  2009-04-08
Journal Detail:
Title:  Dose-response : a publication of International Hormesis Society     Volume:  7     ISSN:  1559-3258     ISO Abbreviation:  -     Publication Date:  2009  
Date Detail:
Created Date:  2009-10-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101308899     Medline TA:  Dose Response     Country:  United States    
Other Details:
Languages:  eng     Pagination:  247-69     Citation Subset:  -    
Institute of Neuroscience and Physiology, Department of Pharmacology, Sahlgrenska Academy at University of Gothenburg, SE-405 30 Gothenburg, Sweden and Discovery DMPK & BAC, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
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