Pharmacokinetic study of rosuvastatin in males and females

Nazir, Shabnam; Iqbal, Zafar; Shah, Yatrik M.; Ahmad, Lateef; Khan, Abad

doi:10.1007/s13318-014-0211-z

Cited by 10 publications

(12 citation statements)

References 19 publications

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“…15 However, in our studies, no statistical differences of pharmacokinetic characteristics were found between Chinese male and female subjects. 15 However, in our studies, no statistical differences of pharmacokinetic characteristics were found between Chinese male and female subjects.…”

Section: Discussioncontrasting

confidence: 70%

“…Additionally, Nazir et al evaluated gender-based pharmacokinetics differences in Asian subjects (Pakistani) and found the C max and AUC 0-t values of rosuvastatin are significantly higher in women. 15 However, in our studies, no statistical differences of pharmacokinetic characteristics were found between Chinese male and female subjects. A clear food effect was observed in male and female groups as well.…”

Section: Discussioncontrasting

confidence: 70%

“…Food and gender are usually considered to be other factors that can also alter the pharmacokinetic profiles of the drugs, leading to variation in systemic exposure, although pharmacodynamic effects and the pharmacokinetics of rosuvastatin are not influenced by the time of day of the drug administration . Recent studies have found that food or gender may affect the systemic exposure of rosuvastatin. These studies have suggested that dose adjustment may be required in a fasted or fed condition as well as for change of gender.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of Food and Gender on Pharmacokinetics of Rosuvastatin in a Chinese Population Based on 4 Bioequivalence Studies

Chen

Lou

Jiang

et al. 2019

Clinical Pharm in Drug Dev

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The effects of food and gender on the pharmacokinetics of rosuvastatin in healthy Chinese subjects were investigated from 4 bioequivalence studies. These studies were designed as randomized, open-label, and 2-period crossover in both fasting and fed states. A total of 204 subjects were enrolled, 134 men and 70 women. These subjects received a single oral 10-mg dose of rosuvastatin with a 7-day washout between 2 periods. The plasma concentrations were determined using a validated liquid chromatography tandem mass spectrometry method, and pharmacokinetic parameters were calculated by noncompartmental methods. Compared with the fasting condition, administration after a high-fat and high-calorie meal resulted in an approximately 40% reduction of rosuvastatin exposure and a near 50% decrease in absorption rate. Moreover, the apparent clearance was significantly greater in the fed state than that in the fasting state. It was noted that the adverse events incidence is increased by approximately 30% in the fasting state; however, no serious adverse events were observed. Additionally, small differences in pharmacokinetic characteristics were found between male and female subjects. Food effect might be considered for optimal effectiveness and safety of rosuvastatin therapy.

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Section: Discussioncontrasting

confidence: 70%

Section: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

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Effects of Food and Gender on Pharmacokinetics of Rosuvastatin in a Chinese Population Based on 4 Bioequivalence Studies

Chen

Lou

Jiang

et al. 2019

Clinical Pharm in Drug Dev

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“…61 Higher systemic exposure of statins in women was observed for pitavastatin, 78 while there is no gender difference in systemic exposure of pravastatin. 79 For rosuvastatin, one study reported higher AUC and C max in women than in men, 80 while no gender difference was observed for rosuvastatin pharmacokinetics in another study. 81 The gender difference in pharmacokinetics of CQ and the effects of CQ on pharmacokinetics of statins have not been reported.…”

Section: Discussionmentioning

confidence: 98%

Downregulation of Organic Anion Transporting Polypeptide (OATP) 1B1 Transport Function by Lysosomotropic Drug Chloroquine: Implication in OATP-Mediated Drug-Drug Interactions

et al. 2016

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Organic anion transporting polypeptide (OATP) 1B1 mediates the hepatic uptake of many drugs including lipid-lowering statins. Decreased OATP1B1 transport activity is often associated with increased systemic exposure of statins and statin-induced myopathy. Antimalarial drug chloroquine (CQ) is also used for long-term treatment of rheumatoid arthritis and systemic lupus erythematosus. CQ is lysosomotropic and inhibits protein degradation in lysosomes. The current studies were designed to determine the effects of CQ on OATP1B1 protein degradation, OATP1B1-mediated transport in OATP1B1-overexpressing cell line, and statin uptake in human sandwich-cultured hepatocytes (SCH). Treatment with lysosome inhibitor CQ increased OATP1B1 total protein levels in HEK293-OATP1B1 cells and in human SCH as determined by OATP1B1 immunoblot. In HEK293-FLAG-tagged OATP1B1 stable cell line, co-immunofluorescence staining indicated that intracellular FLAG-OATP1B1 is colocalized with lysosomal associated membrane glycoprotein (LAMP)-2, a marker protein of late endosome/lysosome. Enlarged LAMP-2-positive vacuoles with FLAG-OATP1B1 protein retained inside were readily detected in CQ-treated cells, consistent with blocking lysosomal degradation of OATP1B1 by CQ. In HEK293-OATP1B1 cells, without pre-incubation, CQ concentrations up to 100 μM did not affect OATP1B1-mediated [3H]E217G accumulation. However, pre-incubation with CQ at clinically relevant concentration(s) significantly decreased [3H]E217G and [3H]pitavastatin accumulation in HEK293-OATP1B1 cells and [3H]pitavastatin accumulation in human SCH. CQ pretreatment (25 μM, 2 h) resulted in ∼1.9-fold decrease in Vmax without affecting Km of OATP1B1-mediated [3H]E217G transport in HEK293-OATP1B1 cells. Pretreatment with monensin and bafilomycin A1, which also have lysosome inhibition activity, significantly decreased OATP1B1-mediated transport in HEK293-OATP1B1 cells. Pharmacoepidemiologic studies using data from the U.S. Food and Drug Administration Adverse Event Reporting System indicated that CQ plus pitavastatin, rosuvastatin, and pravastatin, which are minimally metabolized by the cytochrome P450 enzymes, led to higher myopathy risk than these statins alone. In summary, the present studies report novel findings that lysosome is involved in degradation of OATP1B1 protein and that pre-incubation with lysosomotropic drug CQ downregulates OATP1B1 transport activity. Our in vitro data in combination with pharmacoepidemiologic studies support that CQ has potential to cause OATP-mediated drug–drug interactions.

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“…High-fat and high-calorie meals resulted in a reduction of rosuvastatin exposure and a decrease in absorption rate of rosuvastatin ( Chen et al, 2020 ), showing the relevance of diet. Sex ( Nazir et al, 2015 ) and drug formulation ( Balakumar et al, 2013 ; Dudhipala and Veerabrahma, 2017 ) are other listed factors that influence pharmacokinetics and/or response to rosuvastatin.…”

Section: Introductionmentioning

confidence: 99%

Serum Predose Metabolic Profiling for Prediction of Rosuvastatin Pharmacokinetic Parameters in Healthy Volunteers

et al. 2021

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Rosuvastatin is a well-known lipid-lowering agent generally used for hypercholesterolemia treatment and coronary artery disease prevention. There is a substantial inter-individual variability in the absorption of statins usually caused by genetic polymorphisms leading to a variation in the corresponding pharmacokinetic parameters, which may affect drug therapy safety and efficacy. Therefore, the investigation of metabolic markers associated with rosuvastatin inter-individual variability is exceedingly relevant for drug therapy optimization and minimizing side effects. This work describes the application of pharmacometabolomic strategies using liquid chromatography coupled to mass spectrometry to investigate endogenous plasma metabolites capable of predicting pharmacokinetic parameters in predose samples. First, a targeted method for the determination of plasma concentration levels of rosuvastatin was validated and applied to obtain the pharmacokinetic parameters from 40 enrolled individuals; then, predose samples were analyzed using a metabolomic approach to search for associations between endogenous metabolites and the corresponding pharmacokinetic parameters. Data processing using machine learning revealed some candidates including sterols and bile acids, carboxylated metabolites, and lipids, suggesting the approach herein described as promising for personalized drug therapy.

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Pharmacokinetic study of rosuvastatin in males and females

Cited by 10 publications

References 19 publications

Effects of Food and Gender on Pharmacokinetics of Rosuvastatin in a Chinese Population Based on 4 Bioequivalence Studies

Effects of Food and Gender on Pharmacokinetics of Rosuvastatin in a Chinese Population Based on 4 Bioequivalence Studies

Downregulation of Organic Anion Transporting Polypeptide (OATP) 1B1 Transport Function by Lysosomotropic Drug Chloroquine: Implication in OATP-Mediated Drug-Drug Interactions

Serum Predose Metabolic Profiling for Prediction of Rosuvastatin Pharmacokinetic Parameters in Healthy Volunteers

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