ArticlePharmaceutical research1995
Evaluation of the uptake of pravastatin by perfused rat liver and primary cultured rat hepatocytes.
Article in Pharmaceutical research, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 42 citations in OpenAlex.
- Effects of High-cholesterol Diet on Pravastatin Disposition in the Perfused Rat Liver.European journal of drug metabolism and pharmacokinetics · 2017Article
- Co-administration of paroxetine and pravastatin causes deregulation of glucose homeostasis in diabetic rats via enhanced paroxetine exposure.Acta pharmacologica Sinica · 2014Article
- Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME.Archives of toxicology · 2013Review
- Simultaneous assessment of uptake and metabolism in rat hepatocytes: a comprehensive mechanistic model.The Journal of pharmacology and experimental therapeutics · 2012Article
- Differential effects of pravastatin and simvastatin on the growth of tumor cells from different organ sites.PloS one · 2011Article
- Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport.Pharmaceutical research · 2002Article
- Inhibition of in vitro metabolism of simvastatin by itraconazole in humans and prediction of in vivo drug-drug interactions.Pharmaceutical research · 2001Article
- Clinical pharmacokinetics of pravastatin: mechanisms of pharmacokinetic events.Clinical pharmacokinetics · 2000Review
- Pharmacokinetic study of the hepatobiliary transport of indomethacin.Pharmaceutical research · 2000Article
- Pravastatin, an HMG-CoA reductase inhibitor, is transported by rat organic anion transporting polypeptide, oatp2.Pharmaceutical research · 1999Article
- Uptake is the rate-limiting step in the overall hepatic elimination of pravastatin at steady-state in rats.Pharmaceutical research · 1996Article
- Recent advances in carrier-mediated hepatic uptake and biliary excretion of xenobiotics.Pharmaceutical research · 1996Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeWe have already demonstrated that the HMG-CoA reductase inhibitor, pravastatin is actively taken up by isolated rat hepatocytes via a multispecific anion transporter (Yamazaki et al., Am. J. Physiol. 264, G36-44, (1993)). We further attempted the quantitative evaluation of this uptake in different experimental systems.
methodsWe have quantified the initial uptake of pravastatin by both primary cultured hepatocytes and by isolated perfused rat liver using the multiple indicator dilution (MID) method.
resultsThe permeability surface area product for the influx (PSinf) of pravastatin evaluated in MID study was comparable with those reported previously in isolated rat hepatocytes and in vivo. Furthermore, the highly concentrative uptake (influx clearance >> efflux clearance) of pravastatin was confirmed by kinetic analysis of the dilution curves obtained in the MID study. On the other hand, the uptake by primary cultured cells was significantly lower than that by isolated cells, and the ability of hepatocytes to take up pravastatin showed a decrease with time in culture (0-96 hr). The Vmax for uptake diminished with increasing time in culture, while no significant change was observed in both Km and nonspecific diffusion clearance.
conclusionsThe MID method in isolated perfused liver which maintains the spatial and anatomical architecture can be used to quantitatively evaluate the initial uptake of pravastatin. Furthermore, the ability of hepatocytes to take up pravastatin is diminished in culture with time and this is caused by a decrease in Vmax.
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