Pharmacokinetics of cyclosporin: influence of rate‐duration profile of an intravenous infusion in renal transplant patients.

Gupta, Suneel; Bakran, Ali; Johnson, Raymond F.; Rowland, Malcolm

doi:10.1111/j.1365-2125.1989.tb05376.x

Cited by 4 publications

(2 citation statements)

References 8 publications

(2 reference statements)

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“…As stated by Gupta and associates, rate of infusion can influence pharmacokinetics of CsA and consequently be associated with (peak) concentration-dependent adverse effects. 7 This fact has also been confirmed in animal studies. 8 Some studies have shown that nephrotoxicity, neurotoxicity, hypertension, and metabolic abnormalities from CsA could be dose or concentration dependent.…”

Section: Discussionmentioning

confidence: 59%

Untitled

2015

Exp Clin Transplant

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Objectives: The use of cyclosporine for graft-versushost disease prophylaxis is a major factor in successful allogeneic hematopoietic stem cell transplantation. However, despite the drug being in clinical practice for more than 3 decades, there is no current global and consistent protocol for its optimal method of administration. In this study, we recorded situations related to cyclosporine administration and associated adverse reactions to aid in the development of more precise future guidelines. Materials and Methods: We monitored 22 candidates for allogeneic stem cell transplant during their hospitalization for a 1-year period, acquiring data recorded from predefined questionnaires prepared according to accredited literature, which included daily clinical and laboratory examinations. Results: Despite active attempts toward adherence to a standard protocol for cyclosporine administration, we found numerous occasions of deviations or mistakes, which may have led to adverse reactions. Conclusions: Our study, as one of the first published "drug utilization evaluations" for cyclosporine in stem cell transplant setting, proposes that educating involved clinical staff regarding a standard method of cyclosporine administration and providing efficient facilities would be highly valuable to implementation of a better practice.

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Section: Discussionmentioning

confidence: 59%

Untitled

2015

Exp Clin Transplant

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“…Blood samples to measure serum creatinine, total bilirubin, and cyclosporine levels were obtained at baseline (8 days before), 1 day before, and days 3,6,10,13,17,20,24, and 27 after allogeneic bone marrow transplantation. Samples were obtained at the same time each day immediately prior to initiation of the cyclosporine infusion.…”

Section: Study Protocolmentioning

confidence: 99%

Therapeutic Drug Monitoring of Cyclosporine‐Lipoprotein Levels

Yau,

Brunner,

Lopez‐Berestein

et al. 1991

Pharmacotherapy

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Cyclosporine therapy is complicated by nephrotoxicity that is not predicted by drug levels. In this study serial trough blood samples were obtained from 11 allogeneic marrow transplant recipients after initiation of intravenous cyclosporine 2 mg/kg every 12 hours for a period extending 4 weeks after transplantation. Renal dysfunction, assessed by an increase in serum creatinine levels to twice baseline values or when greater than 175 μmol/L, was found in four patients. No associations between renal dysfunction and cyclosporine levels in whole blood, total plasma, or lipoprotein fractions were found. The ratios of maximum and mean high‐density low‐density lipoprotein cyclosporine concentrations were greatest in patients with renal dysfunction (p < 0.001). The data suggest therapeutic drug monitoring of cyclosporine in various biologic fluids does not predict onset of drug‐associated renal dysfunction. However, the relative role of high‐density to low‐density lipoprotein transport of cyclosporine may provide an index of renal functional changes associated with the agent.

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Effect of Food on the Pharmacokinetics of Cyclosporine in Healthy Subjects Following Oral and Intravenous Administration

Gupta

Manfro

Tomlanovich

et al. 1990

The Journal of Clinical Pharma

111

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The pharmacokinetics of cyclosporine were studied in healthy subjects following administration of cyclosporine both orally (10 mg kg-1) and intravenously (4 mg kg-1) without and with high fat meals. Both blood and plasma samples (separated at 37 degrees C) were analyzed for cyclosporine concentration. Blood and plasma clearances of cyclosporine were calculated to be 0.36 and 0.47 L hr-1 Kg-1, respectively, and volume of distribution at steady state was calculated to be 1.21 L Kg-1, when cyclosporine was administered without a high fat meal. Using plasma analysis, the oral bioavailability of cyclosporine was estimated to be 21 and 79%, when administered without and with a high fat meal, respectively. When cyclosporine was administered intravenously together with a high fat meal, both clearance and volume of distribution increased significantly. Blood and plasma clearances of cyclosporine were 0.44 and 0.70 L hr-1 Kg-1, respectively, when cyclosporine was administered along with a high fat meal. We conclude that food not only enhances the absorption of cyclosporine but also enhances its clearance and volume of distribution. The observed variability in clearance, bioavailability, and volume of distribution values for cyclosporine across various pharmacokinetic studies can be partially accounted by the type of food administered and the sampling matrix used for analysis.

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Pharmacokinetics of cyclosporin: influence of rate‐duration profile of an intravenous infusion in renal transplant patients.

Abstract: 1 The pharmacokinetics of cyclosporin were studied in six renal transplant patients, following intravenous administration of 5 mg kg-' infused over 3, 6 and 24 h.

Cited by 4 publications

References 8 publications

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Therapeutic Drug Monitoring of Cyclosporine‐Lipoprotein Levels

Effect of Food on the Pharmacokinetics of Cyclosporine in Healthy Subjects Following Oral and Intravenous Administration

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