Pharmakokinetik von Mycophenolatmofetil nach primärer orthotoper Herztransplantation – Entwicklung von Kurzalgorithmen zur therapeutischen Arzneimittelüberwachung–
Beschreibung
vor 14 Jahren
Pharmacokinetics of mycophenolate mofetil (MMF) show large
interindividual variability. Concentration-controlled dosing of MMF
based on routine therapeutic drug monitoring, which requires area
under the concentration-time curve (mycophenolic acid
[MPA]-AUC0-12h) determinations, is uncommon. Dose adjustments are
based on predose concentrations (C0h) or side effects. The aim of
this study was to compare C0h with postdose concentrations
(C0.5h-C12h) and to develop practical methods for estimation of
MPA-AUCs on the basis of a limited sampling strategy (LSS) in heart
transplant recipients under MMF and tacrolimus maintenance
immunosuppression. Full MPA-AUC0-12h profiles were generated by
high-performance liquid chromatography in 28 patients. Statistical
analysis for MPA-AUC0-12h was performed by a case resampling
bootstrap method. Bland and Altmann analysis was performed to test
agreement between "predicted AUC" and "measured AUC." C1h provided
the highest coefficient of determination (r2 = 0.57) among the
concentrations determined during the 12-hour interval, which were
correlated with AUC. All other MPA levels were better surrogates of
the MPA-AUC0-12h when compared with C0h (r2 = 0.14). The best
estimation of MPA-AUC0-12h was achieved with four sampling points
with the algorithm AUC = 1.25*C1h + 5.29*C4h + 2.90*C8h + 3.61*C10h
(r2 = 0.95). Since LSS with four time points appeared unpractical,
the authors prefer models with three or two points. To optimize
practicability, LSS with sample points within the first 2 hours
were evaluated resulting in the algorithms: AUC = 1.09*C0.5h +
1.19*C1h + 3.60*C2h (r2 = 0.84) and AUC = 1.65*C0.5h + 4.74*C2h (r2
= 0.75) for three and two sample points, respectively. The results
provide strong evidence for the use of either LSS or the use of
time points other than C0h for therapeutic drug monitoring of MMF.
Using the algorithms for the estimation of MPA-AUC0-12h based on
LSS within the first 2 hours after MMF dosing may help to optimize
treatment with MMF by individualization of dosing.
interindividual variability. Concentration-controlled dosing of MMF
based on routine therapeutic drug monitoring, which requires area
under the concentration-time curve (mycophenolic acid
[MPA]-AUC0-12h) determinations, is uncommon. Dose adjustments are
based on predose concentrations (C0h) or side effects. The aim of
this study was to compare C0h with postdose concentrations
(C0.5h-C12h) and to develop practical methods for estimation of
MPA-AUCs on the basis of a limited sampling strategy (LSS) in heart
transplant recipients under MMF and tacrolimus maintenance
immunosuppression. Full MPA-AUC0-12h profiles were generated by
high-performance liquid chromatography in 28 patients. Statistical
analysis for MPA-AUC0-12h was performed by a case resampling
bootstrap method. Bland and Altmann analysis was performed to test
agreement between "predicted AUC" and "measured AUC." C1h provided
the highest coefficient of determination (r2 = 0.57) among the
concentrations determined during the 12-hour interval, which were
correlated with AUC. All other MPA levels were better surrogates of
the MPA-AUC0-12h when compared with C0h (r2 = 0.14). The best
estimation of MPA-AUC0-12h was achieved with four sampling points
with the algorithm AUC = 1.25*C1h + 5.29*C4h + 2.90*C8h + 3.61*C10h
(r2 = 0.95). Since LSS with four time points appeared unpractical,
the authors prefer models with three or two points. To optimize
practicability, LSS with sample points within the first 2 hours
were evaluated resulting in the algorithms: AUC = 1.09*C0.5h +
1.19*C1h + 3.60*C2h (r2 = 0.84) and AUC = 1.65*C0.5h + 4.74*C2h (r2
= 0.75) for three and two sample points, respectively. The results
provide strong evidence for the use of either LSS or the use of
time points other than C0h for therapeutic drug monitoring of MMF.
Using the algorithms for the estimation of MPA-AUC0-12h based on
LSS within the first 2 hours after MMF dosing may help to optimize
treatment with MMF by individualization of dosing.
Weitere Episoden
Kommentare (0)