The role of lipoproteins in the transport and uptake of cyclosporine and dihydro-tacrolimus into HepG2 and JURKAT cell lines.
OBJECTIVE
We wish to examine the role of lipoproteins in the transport and cellular uptake of cyclosporine (CsA) and tacrolimus.


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.
Rifai
N
N
Department of Laboratory Medicine, Children's Hospital, Boston, MA, USA.
Chao
F F
FF
Pham
Q
Q
Thiessen
J
J
Soldin
S J
SJ
D001693:Biological Transport, Active; D002460:Cell Line; D016572:Cyclosporine / Q000493:pharmacokinetics*; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism; D016559:Tacrolimus / Q000493:pharmacokinetics*; D014316:Tritium
D007166:Immunosuppressive Agents; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008079:Lipoproteins, VLDL; D014316:Tritium; D016572:Cyclosporine; D016559:Tacrolimus