ArticlePharmaceutical research1996
Uptake is the rate-limiting step in the overall hepatic elimination of pravastatin at steady-state in rats.
Article in Pharmaceutical research, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Rosuvastatin pharmacokinetics and pharmacogenetics in Caucasian and Asian subjects residing in the United States.European journal of clinical pharmacology · 2015Trial
- Inhibition of the organic anion-transporting polypeptide 1B1 by quercetin: an in vitro and in vivo assessment.British journal of clinical pharmacology · 2012Trial
- Hepatic clearance, but not gut availability, of erythromycin is altered in patients with end-stage renal disease.Clinical pharmacology and therapeutics · 2010Trial
- Understanding Coproporphyrins and Their Disposition: Coproporphyrinuria is Common, of Diverse Cause, and Rarely Indicates Porphyria.The American journal of medicine · 2025Review
- Mechanisms of altered hepatic drug disposition during pregnancy: small molecules.Expert opinion on drug metabolism & toxicology · 2025Review
- Physiologically Based Pharmacokinetic Modelling to Predict Pharmacokinetics of Enavogliflozin, a Sodium-Dependent Glucose Transporter 2 Inhibitor, in Humans.Pharmaceutics · 2023Article
- The Impact of Suboptimal 25-Hydroxyvitamin D Levels and Cholecalciferol Replacement on the Pharmacokinetics of Oral Midazolam in Control Subjects and Patients With Chronic Kidney Disease.Journal of clinical pharmacology · 2022Article
- The Role of Structure and Biophysical Properties in the Pleiotropic Effects of Statins.International journal of molecular sciences · 2020Review
- Prediction of hepatic clearance in human from in vitro data for successful drug development.The AAPS journal · 2009Review
- The effect of chronic renal failure on drug metabolism and transport.Expert opinion on drug metabolism & toxicology · 2008Review
- Influence of drug transporter polymorphisms on pravastatin pharmacokinetics in humans.Pharmaceutical research · 2007Review
- Conceptual foundations of the UCSD Statin Study: a randomized controlled trial assessing the impact of statins on cognition, behavior, and biochemistry.Archives of internal medicine · 2004 · on this mapReview
- Mean hepatic recovery ratio in capacity-limited first-pass effect by three-point sampling method.Journal of pharmacokinetics and pharmacodynamics · 2003Article
- Clinical pharmacokinetics of pravastatin: mechanisms of pharmacokinetic events.Clinical pharmacokinetics · 2000Review
- Determination of the rate-limiting step in the hepatic elimination of YM796 by isolated rat hepatocytes.Pharmaceutical research · 1999Article
- Analysis of nonlinear hepatic clearance of a cyclopentapeptide, BQ-123, with the multiple indicator dilution method using the dispersion model.Pharmaceutical research · 1999Article
- Membrane transport in hepatic clearance of drugs. I: Extended hepatic clearance models incorporating concentration-dependent transport and elimination processes.Pharmaceutical research · 1997Article
- Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences.Clinical pharmacokinetics · 1997Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeOf the HMG-CoA reductase inhibitors, the hydrophilic pravastatin has been shown to exhibit relatively specific inhibition of cholesterol synthesis in the liver. As one of the reasons for this relatively specific pharmacological activity, we demonstrated that the tissue distribution of pravastatin is limited because of its high hydrophilicity, while hepatic uptake by active transport takes place at the liver surface via a multispecific anion transporter (M. Yamazaki et al., Am. J. Physiol., 264, G36-44, 1993). In this study, we examined the hepatic elimination of pravastatin at steady-state.
methodsAfter i.v. infusion, the plasma concentrations of pravastatin in both arterial and hepatic venous blood were measured.
resultsThe hepatic availability at steady-state exhibited a clear increase on increasing the infusion rate of pravastatin. The total hepatic elimination rate at steady-state exhibited Michaelis-Menten type saturation with the drug concentration in the capillary defined by typical mathematical models (i.e., well-stirred, parallel-tube and dispersion models), K(m) and Vmax values being comparable with those obtained from analysis of the initial uptake velocity using in vitro isolated hepatocytes.
conclusionsThese results indicate that overall hepatic intrinsic clearance of pravastatin at steady-state is regulated by the uptake process, followed by rapid metabolism and/or biliary excretion with minimal efflux to the circulating blood.
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