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Pharmacokinetic alterations in poloxamer 407-induced hyperlipidemic rats

Title
Pharmacokinetic alterations in poloxamer 407-induced hyperlipidemic rats
Authors
Lee, UnjiKwon, Mi HyeKang, Hee Eun
Ewha Authors
이윤지
SCOPUS Author ID
이윤지scopus
Issue Date
2019
Journal Title
XENOBIOTICA
ISSN
0049-8254JCR Link

1366-5928JCR Link
Citation
XENOBIOTICA vol. 49, no. 5, pp. 611 - 625
Keywords
Pharmacokineticshyperlipidemic ratsdrug-metabolizing enzymestransportersprotein binding
Publisher
TAYLOR &

FRANCIS LTD
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Review
Abstract
Plasma lipid profile abnormalities in hyperlipidemia can potentially alter the pharmacokinetics of a drug in a complex manner. To evaluate these pharmacokinetic alterations in hyperlipidemia and to determine the underlying mechanism(s), poloxamer 407-induced hyperlipidemic rats (HL rats), a well-established animal model of hyperlipidemia have been used. In this review, we summarize findings on the pathophysiological and gene expression changes in drug-metabolizing enzymes and transporters in HL rats. We discuss pharmacokinetic changes in drugs metabolized primarily via hepatic cytochrome P450 (CYPs) in terms of alterations in hepatic intrinsic clearance (CLint '), free fraction in plasma (f(u)) and hepatic blood flow rate (Q(H)), depending on the hepatic excretion ratio, as well as drugs eliminated primarily by mechanisms other than hepatic CYPs. For lipoprotein-bound drugs, increased binding to lipoproteins resulted in lower f(u) values and volumes of distribution, with some exceptions. Generally, slower non-renal clearance (or total body clearance) of drugs that are substrates of hepatic CYP3A and CYP2C is well explained by the following factors: alterations in CLint ' (due to down-regulation of hepatic CYPs), decreased f(u) and/or possible decreased Q(H). These consistent findings across studies in HL rats suggest more studies are needed at the clinical level for optimal pharmacotherapies for hyperlipidemia.
DOI
10.1080/00498254.2018.1466212
Appears in Collections:
연구기관 > 약학연구소 > Journal papers
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