Current opinion in nephrology and hypertension · 2002
New concepts in cyclosporine monitoring.
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Keown Paul A
Аннотация
PURPOSE OF REVIEW: Inadequate cyclosporine exposure is a key risk factor for acute rejection, and may contribute to the development of chronic rejection and graft failure. Pre-dose monitoring does not accurately measure drug exposure because of extensive inter- and intra-patient variability in cyclosporine absorption and metabolism. Limited sampling, using individual timed specimens, offers a new, simple and accurate alternative for clinical monitoring of cyclosporine.
RECENT FINDINGS: The area under the first 4 h of the concentration-time curve (AUC ) and the single-point concentration at 2 h post-dose (C2) are key measures of cyclosporine exposure. De novo studies show that achieving an AUC value of more than 4400 microg.h/l or a C2 level of 1500-2000 microg/l during the first 5 days post-transplant minimizes the risk of rejection and improves graft function. Maintenance studies suggest that reducing the C2 level to approximately 800 microg/l after 3-6 months may improve the serum creatinine level, blood pressure, general well-being and reduce adverse effects.
SUMMARY: Single-point C2 monitoring can be implemented quickly and simply with appropriate site and patient training. The timing of phlebotomy is more critical, but immunoassay bias is lower with 2 h post-dose than with trough level measures. Single-point C2 monitoring may be effective in liver and heart replacement, but initial target levels for liver transplantation are lower because cyclosporine is transported directly to the liver via the portal system. C2 monitoring is now being widely adopted as an accurate and practical measure of drug exposure, and can be combined with pharmacodynamic methods to optimize immunosuppression.
RECENT FINDINGS: The area under the first 4 h of the concentration-time curve (AUC ) and the single-point concentration at 2 h post-dose (C2) are key measures of cyclosporine exposure. De novo studies show that achieving an AUC value of more than 4400 microg.h/l or a C2 level of 1500-2000 microg/l during the first 5 days post-transplant minimizes the risk of rejection and improves graft function. Maintenance studies suggest that reducing the C2 level to approximately 800 microg/l after 3-6 months may improve the serum creatinine level, blood pressure, general well-being and reduce adverse effects.
SUMMARY: Single-point C2 monitoring can be implemented quickly and simply with appropriate site and patient training. The timing of phlebotomy is more critical, but immunoassay bias is lower with 2 h post-dose than with trough level measures. Single-point C2 monitoring may be effective in liver and heart replacement, but initial target levels for liver transplantation are lower because cyclosporine is transported directly to the liver via the portal system. C2 monitoring is now being widely adopted as an accurate and practical measure of drug exposure, and can be combined with pharmacodynamic methods to optimize immunosuppression.