Uptake of HMG-CoA reductase inhibitor ZD4522 into hepatocytes and distribution into liver and other tissues of the rat

The relationship between statins and breast cancer prognosis varies by statin type and exposure time: a meta-analysis

“…This hypothesis is supported by the finding that lipophilic statins significantly inhibited the growth of mouse mammary carcinoma cells while hydrophilic statins did not [27]. One pharmacokinetic study confirmed that the hepatocyte selectivity of hydrophilic statins was greater than that of lipophilic statins for unknown reasons [28], which indicates that reduced statin uptake by non-hepatic tissues could limit the protective function of statins. These observations are consistent with our results.…”

New statins and new doses of older statins

“…Two new statins are now in clinical development in various parts of the world [1•,2•, [3][4][5][6]. The most advanced in terms of worldwide development is rosuvastatin (ZD 4522; AstraZeneca Pharmaceuticals, Cheshire, United Kingdom), which is in Phase III trials and projected to be available for general use with in the next 2 years.…”

“…Originally discovered by Shionogi Company, Osaka, Japan, the drug was licensed to AstraZeneca in 1998. It is highly hepatoselective, relatively hydrophilic, and has minimal, if any, metabolism via cytochrome P450 3A4 system (Table 3) [3]. Similar to atorvastatin, ZD 4522 has a relatively long half-life of about 20 hours.…”

Quantitative determination of rosuvastatin in human plasma by ion pair liquid–liquid extraction using liquid chromatography with electrospray ionization tandem mass spectrometry

“…Rosuvastatin is a hepato-selective drug, with selectivity achieved through active transport processes into the liver [3][4][5]. Compared with several other HMG-CoA reductase inhibitors, rosuvastatin does not appear to be metabolized significantly by cytochrome P450 3A4 [6] and, therefore, may not possess the same potential for drug interactions as seen for some other statins.…”

“…Serum protein binding of rosuvastatin was around 88% [8], and the absolute oral bioavailability of rosuvastatin was around 20% [8]. It was found that organic anion transporting polypeptide 1B1 (SLCO1B1) contributes to the hepatic uptake of rosuvastatin [3,9]. But no association was found between the pharmacokinetics of rosuvastatin and genetic variation in SLCO1B1 in Asians [10].…”