Uptake of rosuvastatin by isolated rat hepatocytes: comparison with pravastatin

@article{Nezasa2003UptakeOR,
  title={Uptake of rosuvastatin by isolated rat hepatocytes: comparison with pravastatin},
  author={Ken-ichi Nezasa and Kazutaka Higaki and Masaharu Takeuchi and Masayuki Nakano and Masahiro Koike},
  journal={Xenobiotica},
  year={2003},
  volume={33},
  pages={379 - 388}
}
1. The liver is the target organ for the lipid-regulating effect of rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, and liver-selective uptake of this drug is therefore a desirable property. The uptake kinetics of rosuvastatin were investigated and compared with those of pravastatin using isolated rat hepatocytes. 2. Uptake for both drugs involved both active transport and passive diffusion processes. The Michaelis constant (K m) of uptake rate for rosuvastatin (9… 

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References

SHOWING 1-10 OF 24 REFERENCES

Liver-specific distribution of rosuvastatin in rats: comparison with pravastatin and simvastatin.

TLDR
The results of this study indicated that rosuvastatin was taken up by hepatic cells more selectively and more efficiently than pravastatin and simVastatin.

Carrier-mediated uptake of pravastatin by rat hepatocytes in primary culture.

Na(+)-independent multispecific anion transporter mediates active transport of pravastatin into rat liver.

TLDR
It is demonstrated that the hepatic uptake of pravastatin occurs via a carrier-mediated active transport mechanism utilizing the so-called multispecific anion transporter, which is common with the Na(+)-independent bile acid uptake system, and that this is one of the mechanisms for its selective inhibition of hepatic cholesterol synthesis in vivo.

Pravastatin, an HMG-CoA Reductase Inhibitor, Is Transported by Rat Organic Anion Transporting Polypeptide, oatp2

TLDR
Whether a newly cloned organic anion transporting polypeptide (oatp2) transports pravastatin is examined, and the cloned oatp2 was identified as the transporter responsible for the active hepatocellular pravastsatin uptake.

Preclinical and clinical pharmacology of Rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.

Pharmacokinetics and disposition of rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in rat

TLDR
Results clarified that rosuvastatin selectively distributed in the liver - the target organ - and was excreted in the bile mainly as the unchanged compound.

Uptake of organic anions by isolated rat hepatocytes. A classification in terms of ATP-dependency.

Transport and binding of methotrexate in vivo.

TLDR
This mathematical model is used to interpret data on the uptake of methotrexate in bone marrow, spleen, and small intestine of the bile-cannulated rat following intravenous doses of 0.05,0.25, 2.5, and 25 mg./kg.

Preparation of rat liver cells. II. Effects of ions and chelators on tissue dispersion.

  • P. Seglen
  • Biology
    Experimental cell research
  • 1973