Plasma Distribution of Cyclosporine Within Lipoproteins and “In Vitro” Transfer Between Very-Low-Density Lipoproteins, Low-Density Lipoproteins, and High-Density Lipoproteins

Ta, Hughes; Gaber, A. Osama; Ce, Montgomery

doi:10.1097/00007691-199107000-00002

Cited by 33 publications

(17 citation statements)

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“…37 The interaction of CSA with LDL and HDL has been shown to signi®cantly reduce the renal clearance and extent of renal tissue distribution of the drug in an isolated perfused rat kidney model. 20 The cellular uptake of CSA may be mediated through hepatic HDL 21 and LDL receptors. 22 However, recent work by Rifai et al has shown that despite signi®cant association of CSA with HDL and LDL, these lipoproteins may not serve as vehicles for the cellular uptake of CSA into hepatic-derived cells.…”

Section: Discussionmentioning

confidence: 99%

“…24,25 CSA associates extensively with VLDL, LDL, and HDL. 13,15,21,26 However, no studies to date have thoroughly investigated the in¯uence of lipoproteins on the toxicity and uptake of CSA in a renal cell line. The current studies investigate the effects of lipoproteins on CSA-induced renal toxicity in the pig epithelial cell line LLC-PK 1 .…”

Section: Introductionmentioning

confidence: 99%

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Effects of lipoproteins on cyclosporine a toxicity and uptake in LLC‐PK1 pig kidney cells

Peteherych

2001

Journal of Pharmaceutical Sciences

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of lipoproteins on cyclosporine a toxicity and uptake in LLC‐PK1 pig kidney cells

Peteherych

2001

Journal of Pharmaceutical Sciences

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“…The higher blood concentrations are a reflection that in blood half of CyA is bound to erythrocytes. Of the remainder, much is bound to plasma proteins, especially lipoproteins (Hughes et al, 1991). Based on the positive validation results in plasma, we in turn performed an intraday validation in whole blood, which yielded similar results to those in plasma.…”

Section: Discussionmentioning

confidence: 99%

An analytical method for cyclosporine using liquid chromatography–mass spectrometry

Kanduru

Somayaji

Lavasanifar

et al. 2009

Biomedical Chromatography

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A liquid chromatographic mass spectrometric (LC-MS) assay has been developed for cyclosporine A (CyA) in rat plasma using amiodarone as internal standard (IS). Rat plasma (100 microL) containing drug and IS were extracted using liquid-liquid extraction with 4 mL of 95:5 ether:methanol. After evaporation of the organic layer the residue was reconstituted with 500 microL of water. Then the aqueous layer was transferred to LC-MS sample vials. A 10 microL volume was injected. The analysis was performed on a C(8) column 3.5 microm (2.1 x 50 mm) heated to 60 degrees C with a mobile phase consisting of acetonitrile:methanol:0.2% NH(4)OH (60:20:20) at an isocratic flow-rate of 0.2 mL/min. The ions used for quantitation of CyA and IS were m/z 1202.8 and 645.9, with retention times of 3.35 and 4.72 min, respectively. Linear relationships (r(2) > 0.99) were achieved between plasma or blood concentration and peak height ratios (drug:IS) over the concentration range 50-5000 ng/mL. The CV% and mean error were <19%. Based on validation data, the lower limit of quantification for the assay was 50 ng/mL. The reported assay method displayed high measures of linearity, sensitivity, reliability and precision, allowing its applicability in pharmacokinetic studies in rat.

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“…These results suggest that the transfer of CSA from LDL to HDL is partially facilitated by CETP, while the transfer of CSA from HDL to LDL is facilitated not by CETP but by other plasma factors and/or by spontaneous transfer. This notion is supported by the work of Hughes et al, who hypothesize that the plasma distribution of CSA is determined by factors other than simple diffusion between lipoprotein particles 24 . These findings suggest that the distribution/redistribution of CSA among plasma lipoproteins facilitated by CETP may serve as a possible mechanism for determining the ultimate fate of these compounds.…”

mentioning

confidence: 79%

“…been suggested that cellular uptake of CSA may be mediated through hepatic HDL 24 and LDL receptors 26 , although others have reported that lipoproteins may not serve as vehicles for cellular uptake of CSA into hepaticderived cells 27 . It has been suggested that CSA availability to tissue, and hence its pharmacological or toxic effects, may depend on the lipoprotein with which CSA is associated 9 .…”

Section: Cellular Uptake and Toxicity Studies It Hasmentioning

confidence: 99%

Role of plasma lipoproteins in modifying the toxic effects of water-insoluble drugs: Studies with cyclosporine A

Ramaswamy

Kwong

Boulanger

2002

AAPS J

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Lipoproteins are a heterogeneous population of macromolecular aggregates of lipids and proteins that are responsible for the transport of lipids through the vascular and extravascular fluids from their site of synthesis or absorption to peripheral tissues. Lipoproteins are involved in other biological processes as well, including coagulation and tissue repair, and serve as carriers of a number of hydrophobic compounds within the systemic circulation. It has been well documented that disease states (eg, AIDS, diabetes, cancer) significantly influence circulating lipoprotein content and composition. Therefore, it appears possible that changes in the lipoprotein profile would affect not only the ability of a compound to associate with lipoproteins but also the distribution of the compound within the lipoprotein subclasses. Such an effect could alter the pharmacokinetics and pharmacological action of the drug. This paper reviews the factors that i nfluence the interaction of one model hydrophobic compound, cyclosporine A, with lipoproteins and the implications of altered plasma lipoprotein concentrations on the pharmacological behavior of this compound.

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Plasma Distribution of Cyclosporine Within Lipoproteins and “In Vitro” Transfer Between Very-Low-Density Lipoproteins, Low-Density Lipoproteins, and High-Density Lipoproteins

Cited by 33 publications

References 0 publications

Effects of lipoproteins on cyclosporine a toxicity and uptake in LLC‐PK1 pig kidney cells

Effects of lipoproteins on cyclosporine a toxicity and uptake in LLC‐PK1 pig kidney cells

An analytical method for cyclosporine using liquid chromatography–mass spectrometry

Role of plasma lipoproteins in modifying the toxic effects of water-insoluble drugs: Studies with cyclosporine A

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