Prediction of intravenous cyclosporine area under the concentration-time curve after allogeneic stem cell transplantation

N. Duncan, C. Craddock, M. Cook, S. Nagra, J. Arazzi, Alison H. Thomson

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Currently, routine monitoring of cyclosporine in patients undergoing allogeneic stem cell transplantation is based on analysis of trough, or C0, predose concentrations. However, recent studies in solid organ transplant recipients have demonstrated that monitoring cyclosporine exposure by analyzing 2-hour postdose concentrations (C2) or area under the concentration-time curve (AUC) may improve clinical outcome. This study investigated the ability of single samples to predict exposure to intravenous cyclosporine in eight patients undergoing allogeneic stem cell transplantation. Patients received cyclosporine at a starting dose of 2.5 mg/kg 12-hourly by intravenous infusion over 4 hours. Blood samples were taken at 0, 1, 2, 3, 4, 4.17, 4.33, 4.67, 5, 6, 8, and 12 hours after the start of the infusion. Linear regression was undertaken to investigate the relationship between AUC and concentrations measured at individual time points; bias and precision were also examined. Cyclosporine doses ranged from 250 mg to 430 mg/day, AUC from 3.85 to 8.39 mg.h/L, clearance from 19.1 to 48.1 L/h, and elimination half-life from 3.7 to 15.5 hours. Although C-max and the concentration measured at 3 hours (C3) provided the best prediction of AUC (r(2) = 0.90 and r(2) = 0.87, respectively), the infusion protocol made the time of Cmax difficult to predict. Concentrations measured at the end of the infusion (Cend) and 12 hours postdose (C12) gave similar results (r(2) = 0.87 and 0.77, respectively). These data suggest that C12 concentrations provide an acceptable marker of total exposure to intravenous cyclosporine in patients undergoing allogeneic stem cell transplantation
LanguageEnglish
Pages353-358
Number of pages6
JournalTherapeutic Drug Monitoring
Volume32
Issue number3
DOIs
Publication statusPublished - Jun 2010

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Stem Cell Transplantation
Cyclosporine
Intravenous Infusions
Half-Life
Linear Models
Transplants

Keywords

  • therapeutic drug monitoring
  • immunosuppressants
  • pharmacokinetics

Cite this

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title = "Prediction of intravenous cyclosporine area under the concentration-time curve after allogeneic stem cell transplantation",
abstract = "Currently, routine monitoring of cyclosporine in patients undergoing allogeneic stem cell transplantation is based on analysis of trough, or C0, predose concentrations. However, recent studies in solid organ transplant recipients have demonstrated that monitoring cyclosporine exposure by analyzing 2-hour postdose concentrations (C2) or area under the concentration-time curve (AUC) may improve clinical outcome. This study investigated the ability of single samples to predict exposure to intravenous cyclosporine in eight patients undergoing allogeneic stem cell transplantation. Patients received cyclosporine at a starting dose of 2.5 mg/kg 12-hourly by intravenous infusion over 4 hours. Blood samples were taken at 0, 1, 2, 3, 4, 4.17, 4.33, 4.67, 5, 6, 8, and 12 hours after the start of the infusion. Linear regression was undertaken to investigate the relationship between AUC and concentrations measured at individual time points; bias and precision were also examined. Cyclosporine doses ranged from 250 mg to 430 mg/day, AUC from 3.85 to 8.39 mg.h/L, clearance from 19.1 to 48.1 L/h, and elimination half-life from 3.7 to 15.5 hours. Although C-max and the concentration measured at 3 hours (C3) provided the best prediction of AUC (r(2) = 0.90 and r(2) = 0.87, respectively), the infusion protocol made the time of Cmax difficult to predict. Concentrations measured at the end of the infusion (Cend) and 12 hours postdose (C12) gave similar results (r(2) = 0.87 and 0.77, respectively). These data suggest that C12 concentrations provide an acceptable marker of total exposure to intravenous cyclosporine in patients undergoing allogeneic stem cell transplantation",
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Prediction of intravenous cyclosporine area under the concentration-time curve after allogeneic stem cell transplantation. / Duncan, N.; Craddock, C.; Cook, M.; Nagra, S.; Arazzi, J.; Thomson, Alison H.

In: Therapeutic Drug Monitoring, Vol. 32, No. 3, 06.2010, p. 353-358.

Research output: Contribution to journalArticle

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T1 - Prediction of intravenous cyclosporine area under the concentration-time curve after allogeneic stem cell transplantation

AU - Duncan, N.

AU - Craddock, C.

AU - Cook, M.

AU - Nagra, S.

AU - Arazzi, J.

AU - Thomson, Alison H.

PY - 2010/6

Y1 - 2010/6

N2 - Currently, routine monitoring of cyclosporine in patients undergoing allogeneic stem cell transplantation is based on analysis of trough, or C0, predose concentrations. However, recent studies in solid organ transplant recipients have demonstrated that monitoring cyclosporine exposure by analyzing 2-hour postdose concentrations (C2) or area under the concentration-time curve (AUC) may improve clinical outcome. This study investigated the ability of single samples to predict exposure to intravenous cyclosporine in eight patients undergoing allogeneic stem cell transplantation. Patients received cyclosporine at a starting dose of 2.5 mg/kg 12-hourly by intravenous infusion over 4 hours. Blood samples were taken at 0, 1, 2, 3, 4, 4.17, 4.33, 4.67, 5, 6, 8, and 12 hours after the start of the infusion. Linear regression was undertaken to investigate the relationship between AUC and concentrations measured at individual time points; bias and precision were also examined. Cyclosporine doses ranged from 250 mg to 430 mg/day, AUC from 3.85 to 8.39 mg.h/L, clearance from 19.1 to 48.1 L/h, and elimination half-life from 3.7 to 15.5 hours. Although C-max and the concentration measured at 3 hours (C3) provided the best prediction of AUC (r(2) = 0.90 and r(2) = 0.87, respectively), the infusion protocol made the time of Cmax difficult to predict. Concentrations measured at the end of the infusion (Cend) and 12 hours postdose (C12) gave similar results (r(2) = 0.87 and 0.77, respectively). These data suggest that C12 concentrations provide an acceptable marker of total exposure to intravenous cyclosporine in patients undergoing allogeneic stem cell transplantation

AB - Currently, routine monitoring of cyclosporine in patients undergoing allogeneic stem cell transplantation is based on analysis of trough, or C0, predose concentrations. However, recent studies in solid organ transplant recipients have demonstrated that monitoring cyclosporine exposure by analyzing 2-hour postdose concentrations (C2) or area under the concentration-time curve (AUC) may improve clinical outcome. This study investigated the ability of single samples to predict exposure to intravenous cyclosporine in eight patients undergoing allogeneic stem cell transplantation. Patients received cyclosporine at a starting dose of 2.5 mg/kg 12-hourly by intravenous infusion over 4 hours. Blood samples were taken at 0, 1, 2, 3, 4, 4.17, 4.33, 4.67, 5, 6, 8, and 12 hours after the start of the infusion. Linear regression was undertaken to investigate the relationship between AUC and concentrations measured at individual time points; bias and precision were also examined. Cyclosporine doses ranged from 250 mg to 430 mg/day, AUC from 3.85 to 8.39 mg.h/L, clearance from 19.1 to 48.1 L/h, and elimination half-life from 3.7 to 15.5 hours. Although C-max and the concentration measured at 3 hours (C3) provided the best prediction of AUC (r(2) = 0.90 and r(2) = 0.87, respectively), the infusion protocol made the time of Cmax difficult to predict. Concentrations measured at the end of the infusion (Cend) and 12 hours postdose (C12) gave similar results (r(2) = 0.87 and 0.77, respectively). These data suggest that C12 concentrations provide an acceptable marker of total exposure to intravenous cyclosporine in patients undergoing allogeneic stem cell transplantation

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