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Relationships between sirolimus dosing, concentration and outcomes in renal transplant recipients
Author(s) -
Dansirikul C.,
Duffull S. B.,
Morris R. G.,
Tett S. E.
Publication year - 2005
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2005.02473.x
Subject(s) - sirolimus , dosing , medicine , pharmacokinetics , renal transplant , transplantation , pharmacodynamics , population , adverse effect , urology , kidney transplantation , pharmacology , environmental health
Aim To explore relationships between sirolimus dosing, concentration and clinical outcomes. Methods Data were collected from 25 kidney transplant recipients (14 M/11 F), median 278 days after transplantation. Outcomes of interest were white blood cell (WBC) count, platelet (PLT) count, and haematocrit (HCT). A naive pooled data analysis was performed with outcomes dichotomized (Mann–Whitney U ‐tests). Results Several patients experienced at least one episode when WBC ( n = 9), PLT ( n = 12), or HCT ( n = 21) fell below the lower limits of the normal range. WBC and HCT were significantly lower ( P < 0.05) when sirolimus dose was greater than 10 mg day −1 , and sirolimus concentration greater than 12 µg l −1 . No relationship was shown for PLT and dichotomized sirolimus dose or concentration. Conclusions Given this relationship between sirolimus concentration and effect, linked population pharmacokinetic–pharmacodynamic modelling using data from more renal transplant recipients should now be used to quantify the time course of these relationships to optimize dosing and minimize risk of these adverse outcomes.