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…
94 Citations
Kinetic Characterization of Rat Hepatic Uptake of 16 Actively Transported Drugs
- BiologyDrug Metabolism and Disposition
- 2011
Assessment of the role of active uptake relative to the passive process indicated that, at low concentrations, the active process contributes >80% to the overall uptake for 13 drugs, and high passive permeability dominates over transporter-mediated uptake for saquinavir over the full concentration range.
Murine Oatp1a/1b Uptake Transporters Control Rosuvastatin Systemic Exposure Without Affecting Its Apparent Liver Exposure
- Biology, MedicineMolecular Pharmacology
- 2013
Absence of Oatp1a/1b uptake transporters increases the systemic exposure of rosuvastatin by reducing its hepatic extraction ratio, but liver concentrations are not significantly affected.
Detection of statin cytotoxicity is increased in cells expressing the OATP1B1 transporter.
- Biology, ChemistryToxicological sciences : an official journal of the Society of Toxicology
- 2013
The data suggested that uptake transporters have a significant impact on the outcomes of a cell-based assay and should be considered during the early stages of compound toxicity screening in drug discovery.
Simultaneous Assessment of Uptake and Metabolism in Rat Hepatocytes: A Comprehensive Mechanistic Model
- BiologyJournal of Pharmacology and Experimental Therapeutics
- 2012
Modeling of uptake kinetics in conjunction with metabolism improved the precision of the uptake parameter estimates for repaglinide and telmisartan and reduced the error in certain parameter estimates observed with shorter incubation times.
Multiple Transporters Affect the Disposition of Atorvastatin and Its Two Active Hydroxy Metabolites: Application of in Vitro and ex Situ Systems
- Biology, ChemistryJournal of Pharmacology and Experimental Therapeutics
- 2006
Interaction of ATV with hepatic uptake transporter organic anion transporting polypeptide (Oatp) and efflux transporter multidrug resistance associated protein 2 (MRP2/Mrp2) in vitro and ex situ and inhibition of Oatp-mediated uptake seems to be the major determinant for interaction between ATV and RIF.
Ritonavir and dexamethasone induce expression of CYP3A and P-glycoprotein in rats
- Biology, MedicineXenobiotica; the fate of foreign compounds in biological systems
- 2004
Increased expression of CYP3A isoforms and of P-gp occurs with 3 days of exposure to RIT in rats, and might contribute to drug interactions involving RIT (and other antiretroviral agents) in humans.
Statins and myotoxicity: a therapeutic limitation
- Biology, MedicineExpert opinion on drug safety
- 2006
The present understanding of pathophysiological mechanisms, does not offer a reliable approach to address the same at preclinical level, yet the low incidence of myotoxicty including rhabdomyolysis and less severity of commonly occurring myopathy and myalgia do not raise doubts about the clinical efficacy and tolerability of statins.
Comparison of Methods for Estimating Unbound Intracellular-to-Medium Concentration Ratios in Rat and Human Hepatocytes Using Statins
- Biology, MedicineDrug Metabolism and Disposition
- 2017
Comparison of predictability of the unbound hepatocyte-to-medium concentration ratios by two methods based on the steady-state cell- to-medium total concentration ratios at 37°C and on ice and based on their initial uptake rates suggests that Kp,uu,ss is preferable for estimating the concentration of unbound drugs inside the hepatocytes.
Hepatic Basolateral Efflux Contributes Significantly to Rosuvastatin Disposition I: Characterization of Basolateral Versus Biliary Clearance Using a Novel Protocol in Sandwich-Cultured Hepatocytes
- BiologyThe Journal of Pharmacology and Experimental Therapeutics
- 2013
Alterations in MRP4-mediated RSV CLBL due to drug-drug interactions, genetic polymorphisms, or disease states may lead to changes in hepatic and systemic exposure of RSV, with implications for the safety and efficacy of this commonly used medication.
Transporters as a determinant of drug clearance and tissue distribution.
- BiologyEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
- 2006
References
SHOWING 1-10 OF 24 REFERENCES
Liver-specific distribution of rosuvastatin in rats: comparison with pravastatin and simvastatin.
- Biology, MedicineDrug metabolism and disposition: the biological fate of chemicals
- 2002
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.
- Biology, MedicineBiochemical pharmacology
- 1992
Na(+)-independent multispecific anion transporter mediates active transport of pravastatin into rat liver.
- Biology, ChemistryThe American journal of physiology
- 1993
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
- BiologyPharmaceutical Research
- 2004
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.
- Biology, ChemistryThe American journal of cardiology
- 2001
Pharmacokinetics and disposition of rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in rat
- Biology, ChemistryXenobiotica; the fate of foreign compounds in biological systems
- 2002
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.
- Chemistry, BiologyJournal of hepatology
- 1992
Effect of rosuvastatin on low-density lipoprotein cholesterol in patients with hypercholesterolemia.
- MedicineThe American journal of cardiology
- 2001
Transport and binding of methotrexate in vivo.
- BiologyJournal of pharmaceutical sciences
- 1973
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.
- BiologyExperimental cell research
- 1973