Effects of Plasma Lipid Levels on Blood Distribution and Pharmacokinetics of Cyclosporin A

Gardier, Alain M.; Mathé, Denis; Guedeney, X; Barré, Jérôme; Benvenutti, Christophe; Navarro, Nicole; Vernillet, Laurent; Loisance, D; Cachera, J P; Jacotot, B.; Tillement, Jean‐Paul

doi:10.1097/00007691-199308000-00003

Cited by 44 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…17 The effect of altered lipoprotein levels on the pharmacokinetics of CyA is unclear. Some studies have reported decreases in CL and Vd, [30][31][32][33] although in some cases nonspecifi c radioimmunoassay was used to measure CyA concentrations. It has been shown that in volunteers the CL and Vd of IV-administered CyA are enhanced by the ingestion of a high-fat meal.…”

Section: Discussionmentioning

confidence: 99%

“…32 On the other hand, an in vitro study has suggested that increased VLDL and HDL concentrations could have protective properties against nephrotoxicity and reduce cellular uptake of drug within LLC-PK1 pig kidney cells. 35 The fi nding of increased CyA uptake in kidney after a single IV dose in HL animals ( Table 1 , Figure 1 ), which is in line with previous fi ndings, 32 warranted further study. To explore the signifi cance of the increase in CyA kidney concentrations, the nephrotoxicity experiment was devised and undertaken.…”

Section: E679mentioning

confidence: 99%

See 1 more Smart Citation

Insights into the effects of hyperlipoproteinemia on cyclosporine A biodistribution and relationship to renal function

Aliabadi

Spencer

Mahdipoor

et al. 2006

AAPS J

View full text Add to dashboard Cite

The purpose of this study was to assess the effect of hyperlipoproteinemia on the biodistribution of cyclosporine A (CyA), an extensively lipoprotein bound immunosuppressant, in a rat model and to determine the potential toxicological signifi cance of this effect. Normolipidemic and hyperlipoproteinemic rats were given a single 5 mg/kg dose of CyA as intravenous bolus and at selected times postdose, tissues, blood, and plasma were harvested and assayed for CyA content. Hyperlipoproteinemia was induced by intraperitoneal injection of 1 g/kg poloxamer 407. Compared with normolipidemic animals, hyperlipoproteinemic rats had higher plasma, blood, kidney, and liver CyA concentrations. In contrast, in heart and spleen the concentrations were decreased in hyperlipoproteinemia. The nephrotoxic effect of CyA was also evaluated in normolipidemic and hyperlipoproteinemic rats after 7 days of dosing with 20 mg/kg/day. In both groups of animals, repeated doses of CyA were associated with equivalent decreases in creatinine and urea clearances compared with matching control and predose baseline measures. The concentrations of drug in kidney were equivalent at the conclusion of the study. However, despite these similarities there was microscopic evidence of more severe changes in the kidneys in the hyperlipoproteinemic rats, which also experienced a signifi cant decrease in body weight compared with the normolipedemic animals. In conclusion, the distribution of CyA to kidneys was enhanced in poloxamer 407 -induced hyperlipoproteinemic rats after single doses, and with repeated doses there was an apparent greater adverse effect on these animals compared with normolipidemic animals.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: E679mentioning

confidence: 99%

Insights into the effects of hyperlipoproteinemia on cyclosporine A biodistribution and relationship to renal function

Aliabadi

Spencer

Mahdipoor

et al. 2006

AAPS J

View full text Add to dashboard Cite

show abstract

“…We believe that this property has a major effect on the efficacy and safety of these compounds since they are often administered to patients with abnormal cholesterol metabolism (8,9,12). Disease-related changes in liver and kidney function and blood flow may also alter the pharmacokinetics and toxic effects of these drugs.…”

mentioning

confidence: 99%

Amphotericin B Lipid Complex or Amphotericin B Multiple-Dose Administration to Rabbits with Elevated Plasma Cholesterol Levels: Pharmacokinetics in Plasma and Blood, Plasma Lipoprotein Levels, Distribution in Tissues, and Renal Toxicities

Ramaswamy

Peteherych

Kennedy

2001

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The purpose of the present study was to determine if a relationship exists between the plasma cholesterol concentration, the severity of amphotericin B (AmpB)-induced renal toxicity, and the pharmacokinetics of AmpB in plasma in hypercholesterolemic rabbits administered multiple doses of amphotericin B (AmB) deoxycholate (Doc-AmB) and AmB lipid complex (ABLC). After 7 days of administration of a cholesterolenriched diet (0.50% [wt/vol]) or a regular rabbit diet, each rabbit was administered a single intravenous bolus of Doc-AmB (n ‫؍‬ 8) or ABLC (n ‫؍‬ 10) (1.0 mg/kg of body weight) daily for 7 consecutive days (a total of eight doses). Blood samples were obtained daily before and 24 h after the administration of each dose and serially thereafter following the administration of the last dose for the assessment of pharmacokinetics in plasma, kidney toxicity, plasma lipoprotein levels, and drug distribution in tissue. The pharmacokinetics of AmB in blood following the administration of ABLC were also determined in rabbits fed cholesterol-enriched and regular diets (n ‫؍‬ 3 each group). Before drug treatment, cholesterol-fed rabbits demonstrated marked increases in total, low-density lipoprotein (LDL), and triglyceride-rich lipoprotein (TRL) cholesterol levels in plasma compared with the levels in rabbits on a regular diet. No significant differences in total plasma triglyceride levels were observed. Significant increases in plasma creatinine levels were observed in rabbits fed a cholesterol-enriched diet (P < 0.05) and rabbits fed a regular diet (P < 0.05) when administered AmB. However, the magnitude of this increase was twofold greater in rabbits fed a regular diet than in rabbits fed a cholesterol-enriched diet. An increase in plasma creatinine levels was observed only in rabbits on a cholesterol-enriched diet administered ABLC. The pharmacokinetics of AmB were significantly altered in rabbits on a cholesterol-enriched diet administered Doc-AmB or ABLC compared to those in rabbits on a regular diet administered each of these compounds. The pharmacokinetics of AmB in blood were significantly different following ABLC administration but not following Doc-AmB administration in both rabbits fed cholesterolenriched diets and rabbits fed regular diets compared to their corresponding pharmacokinetics in plasma. An increased percentage of AmB was recovered in the TRL fraction when Doc-AmB was administered to rabbits fed a cholesterol-enriched diet than when it was administered to rabbits fed a regular diet. Furthermore, an increased percentage of AmB was recovered in the LDL and TRL fractions when ABLC was administered to rabbits fed a cholesterol-enriched diet rabbits fed a regular diet. These findings suggest that an increase in plasma cholesterol levels modifies the pharmacokinetics of AmB and renal toxicity following the administration of multiple intravenous doses of Doc-AmB and ABLC.Disseminated fungal infections such as candidiasis, histoplasmosis, and aspergillosis are on the rise, particularly in patients with ...

show abstract

“…In whole blood CsA is primarily transported bound to lipoproteins (33%) and erythrocytes (58%) and whole blood CsA levels correlate with lipoprotein levels [37,38]. In vitro and in vivo studies show that in serum from healthy patients 50-60% of CsA is bound to HDL, 20-30% to LDL, 10-25% to VLDL with 10-15% bound to the non-lipoprotein proteins [39,40,41,42].…”

Section: Interaction Of Csa With Plasma Lipoproteinsmentioning

confidence: 99%

Cyclosporin A-Induced Hyperlipidemia

Kockx¹,

Kritharides²

2012

Lipoproteins - Role in Health and Diseases

View full text Add to dashboard Cite

Effects of Plasma Lipid Levels on Blood Distribution and Pharmacokinetics of Cyclosporin A

Cited by 44 publications

References 0 publications

Insights into the effects of hyperlipoproteinemia on cyclosporine A biodistribution and relationship to renal function

Insights into the effects of hyperlipoproteinemia on cyclosporine A biodistribution and relationship to renal function

Amphotericin B Lipid Complex or Amphotericin B Multiple-Dose Administration to Rabbits with Elevated Plasma Cholesterol Levels: Pharmacokinetics in Plasma and Blood, Plasma Lipoprotein Levels, Distribution in Tissues, and Renal Toxicities

Cyclosporin A-Induced Hyperlipidemia

Contact Info

Product

Resources

About