Pharmacokinetic and pharmacodynamic alterations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors: Drug–drug interactions and interindividual differences in transporter and metabolic enzyme functions

Shitara, Yoshihisa; Sugiyama, Yuichi

doi:10.1016/j.pharmthera.2006.03.003

Cited by 517 publications

(484 citation statements)

References 174 publications

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“…As illustrated extensively by examples of statin family, it is important to understand the role of the active hepatic uptake in drug clearance and its subsequent impact on drug disposition in order to understand the relationship between the intracellular concentration and observed efficacy 1. Organic anion‐transporting polypeptides (OATPs) are well known hepatic uptake transporters, and many statins are known to be substrates of these transporters.…”

mentioning

confidence: 99%

Prediction of the Pharmacokinetics of Pravastatin as an OATP Substrate Using Plateable Human Hepatocytes With Human Plasma Data and PBPK Modeling

Mao¹,

Doshi

Wright³

et al. 2018

CPT Pharmacom & Syst Pharma

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Plateable human hepatocytes with human plasma were utilized to generate the uptake transporter kinetic data for pravastatin, an organic anion‐transporting polypeptide (OATP) transporter substrate. The active hepatic uptake of pravastatin was determined with a Jmax value of 134.4 pmol/min/million cells and Km of 76.77 µM in plateable human hepatocytes with human plasma. The physiologically‐based pharmacokinetic (PBPK) model with incorporation of these in vitro kinetic data successfully simulated the i.v. pharmacokinetic profile of pravastatin without applying scaling factor (the mean predicted area under the curve (AUC) is within 1.5‐fold of the observed). Furthermore, the PBPK model also adequately described the oral plasma concentration‐time profiles of pravastatin at different dose levels. The current investigation demonstrates an approach allowing us to build upon the translation of in vitro OATP uptake transporter data to in vivo, with a hope of utilizing the in vitro data for the prospective human pharmacokinetic (PK) prediction.

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mentioning

confidence: 99%

Prediction of the Pharmacokinetics of Pravastatin as an OATP Substrate Using Plateable Human Hepatocytes With Human Plasma Data and PBPK Modeling

Mao¹,

Doshi

Wright³

et al. 2018

CPT Pharmacom & Syst Pharma

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“…Furthermore, since folate uptake increased with decreases in buffer pH, and nonlabeled folate and its structural analogs had inhibitory effect on folate uptake under both acidic and neutral conditions, these results suggest that folate uptake into BeWo cells is carrier-mediated. However, pravastatin, probenecid, indomethacin, nicotic acid and p-aminohippurate, which have been reported to be substrates or inhibitors of various anion transport mechanisms, [27][28][29][30] had inhibitory effects only under an acidic buffer condition. These results suggest that BeWo cells also have a folate carrier of which the function differed depending on buffer pH.…”

Section: Discussionmentioning

confidence: 99%

The Mechanism of Carrier-Mediated Transport of Folates in BeWo Cells: The Involvement of Heme Carrier Protein 1 in Placental Folate Transport

Yasuda¹,

Hasui²,

Kobayashi³

et al. 2008

Bioscience, Biotechnology, and Biochemistry

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“…5 The oral absorption of ATV is 30% and bioavailability is only 12%. 6 As with other HMG-CoA reductase inhibitors, the most frequently reported adverse events associated with ATV are gastrointestinal effects. 7 In controlled drug delivery systems (DDS) the drug can be transported to the site of action, hence, its effect on vital tissues and minimized undesirable side effects.…”

Section: Introductionmentioning

confidence: 99%

Biochemical and histopathological assessment of atorvastatin-loaded nanoemulsion effectiveness in Rats

Balamash

Al-ddyni

2018

Int J Basic Clin Pharmacol

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Background: Atorvastatin (ATV), a lipid lowering agent, has low solubility and poor dissolution affects its oral bioavailability. Nanoemulsion (NE) has been developed to improve the delivery of therapeutic agents. This study was aimed to assess the ability of the NE in enhancing ATV bioavailability and minimizing its side effects in hyperlipidemic rats.Methods: Thirty-five rats divided into seven groups were utilized in this study. Hyperlipidemia was induced by feeding rats high fat diet (HFD) for 3 months. The antihyperlipidemic activity of 10 and 20 mg/kg of ATV loaded in two different delivery systems; nanoemulsion (10% and 20% ATV-LNE) or in water (10% and 20% ATV-sol), were investigated. At the end of the experiment, body weight, serum and plasma biochemical parameters (lipid profile, glucose, insulin, liver and kidney functions, oxidative stress markers were assessed. Liver and kidney were histopathologically examined. The physical characteristics of NE were determined by the Zetasizer (the z-average diameter and zeta potential).Results: 20% ATV-LNE had the smallest nanoparticles (38.12±6.71nm) whereas it had the largest zeta negative potential of -26.8±4.16mV. The serum biochemical results and the histopathological examination revealed that treatment with 20% ATV-LNE improved the lipid profile by significantly increasing HDL and decreasing cholesterol and low-density lipoprotein. Both 10 and 20% ATV-LNE reduced serum glucose level compared to other used formulas.Conclusions: NE formulas have the potential to improve the bioavailability and efficacy of ATV and reduce its side effects.

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Pharmacokinetic and pharmacodynamic alterations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors: Drug–drug interactions and interindividual differences in transporter and metabolic enzyme functions

Cited by 517 publications

References 174 publications

Prediction of the Pharmacokinetics of Pravastatin as an OATP Substrate Using Plateable Human Hepatocytes With Human Plasma Data and PBPK Modeling

Prediction of the Pharmacokinetics of Pravastatin as an OATP Substrate Using Plateable Human Hepatocytes With Human Plasma Data and PBPK Modeling

The Mechanism of Carrier-Mediated Transport of Folates in BeWo Cells: The Involvement of Heme Carrier Protein 1 in Placental Folate Transport

Biochemical and histopathological assessment of atorvastatin-loaded nanoemulsion effectiveness in Rats

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