The role of lipoproteins in the transport and uptake of cyclosporine and dihydro-tacrolimus into HepG2 and JURKAT cell lines

doi:10.1016/0009-9120(96)00001-X

Clinical Biochemistry

Volume 29, Issue 2, April 1996, Pages 149-155

https://doi.org/10.1016/0009-9120(96)00001-X Get rights and content

Abstract

Objectives: We wish to examine the role of lipoproteins in the transport and cellular uptake of cyclosporine (CsA) and tacrolimus.

Design and Methods: The distribution of tritiated CsA and tacrolimus among lipoproteins was determined in normo- and hypertriglyceridemic sera. The uptake of these two drugs into HepG2 and JURKAT cell lines was assessed in the presence of various concentrations of low density lipoproteins (LDL).

Results: Our data showed that about 60% of these drugs were transported by high density lipoprotein in normolipidemic sera, while about 50–60% were carried by very low density lipoprotein in hypertriglyceridemic sera. Almost 80% of CsA and 70% of tacrolimus entered HepG2 and JURKAT cells within the first hour of incubation in lipoprotein free media. However, the uptake was decreased (CsA by 60% and tacrolimus by 40%) in the presence of LDL.

Conclusions: Lipoproteins play a major role in the transport of CsA and tacrolimus, but not in their cellular uptake.

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AnalyticalThe role of lipoproteins in the transport and uptake of cyclosporine and dihydro-tacrolimus into HepG2 and JURKAT cell lines

Abstract

J Lipid Res

Methods Enzym

J Biol Chem

Biochim Biophys Acta

Inhibition of T-cell activity by cyclosporin A

Scand J Immunol

FK-506, a novel immunosuppressant isolated from a streptomyces. II. Immunosuppressive effect of FK-506 in vitro

J Antibiot

Factors influencing the pharmacokinetics of cyclosporine in man

Ther Drug Monit

Distribution and concentration of cyclosporin in human blood

J Clin Pathol

Distribution and binding of cyclosporine in blood and tissues

Pharmacokinetics of FK 506: Preclinical and clinical studies

Interaction of cyclosporine A with human lipoproteins

J Pharm Pharmacol

Distribution of FK 506 in plasma lipoproteins in transplant patients

Analytical
The role of lipoproteins in the transport and uptake of cyclosporine and dihydro-tacrolimus into HepG2 and JURKAT cell lines