Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/17670
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Type: Journal article
Title: Relationships between sirolimus dosing, concentration and outcomes in renal transplant recipients
Author: Dansirikul, C.
Duffull, S.
Morris, R.
Tett, S.
Citation: British Journal of Clinical Pharmacology, 2005; 60(5):560-565
Publisher: Blackwell Publishing Ltd
Issue Date: 2005
ISSN: 0306-5251
1365-2125
Abstract: <h4>Aim</h4>To explore relationships between sirolimus dosing, concentration and clinical outcomes.<h4>Methods</h4>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).<h4>Results</h4>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 microg l(-1). No relationship was shown for PLT and dichotomized sirolimus dose or concentration.<h4>Conclusions</h4>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.
Keywords: Humans; Hematologic Diseases; Postoperative Complications; Sirolimus; Immunosuppressive Agents; Leukocyte Count; Platelet Count; Hematocrit; Prognosis; Kidney Transplantation; Retrospective Studies; Dose-Response Relationship, Drug; Adult
RMID: 0020051141
DOI: 10.1111/j.1365-2125.2005.02473.x
Appears in Collections:Pharmacology publications

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