Therapeutic Drug Monitoring of Sirolimus, Correlation With Laboratory Parameters In Transplant Patients Therapeutic drug monitoring of sirolimus
Iranian Journal of Pharmaceutical Sciences,
Vol. 7 No. 4 (2011),
1 October 2011
,
Page 237-245
https://doi.org/10.22037/ijps.v7.41303
Abstract
Sirolimus is a potent immunosuppressive agent administered as prophylactic agent to prevent rejection after organ transplantation. Sirolimus must be used within a narrow therapeutic window. Due to inter- and intra-variability, sirolimus blood concentrations may be affected, therefore, there is no possibility of predicting the sirolimus blood concentrations based on the dose patients received. Therapeutic drug monitoring (TDM) of whole blood is an important part of immunosuppressive therapy and is mandatory for sirolimus dosage individualization. The objective of this study was to present a validated method for the analysis of sirolimus in human blood by LC/MS spectrometry and also evaluation of correlation between blood
sirolimus concentration and laboratory parameters. We examined a group of 32 patients receiving sirolimus at different stages after organ (kidney, liver or pancreas) transplantation. The mean sirolimus concentration was 10.2 ng/ml (range: 1.330.1 ng/ml).The assay was validated for a linear dynamic range of 1-50 ng/ml. The correlation coefficient (r) was 0.995. The within-run imprecision CV(%) for concentrations (1 and 10 ng/ml) were 14.7 and 2.2%, respectively. The betweenrun imprecision CV(%) for the same concentrations were 14.8 and 3.4%, respectively. Limit of quantification (LOQ) and limit of detection (LOD) were defined as 1 and 0.3 ng/ml, respectively. Analytic recovery was 98±2% over a range of 1-50 ng/ml. Statistical
results showed no correlation between sirolimus blood concentration and the dosage in patients receiving sirolimus. Also, no relationship between drug concentration in blood and laboratory parameters was seen.
- Immunosuppressive agent
- Sirolimus
- Therapeutic drug monitoring
How to Cite
References
[2] Rosemary L, Hoffmann RN, Tricia Roesch RN. Update on transplant pharmacology, sirolimus. DCCN 2004, 23: 69-75.
[3] French DC, Saltzgueber M, Hicks DR, Cowper AL, Holt DW. HPLC assay with ultraviolet detection for therapeutic drug monitoring of sirolimus. Clin Chem 2001; 47: 1316-9.
[4] Holt DW, Denny K, Lee TD, Johnston A. Therapeutic monitoring of sirolimus: its contribution to optimal prescription. Transplant Proc 2003; 35: 157S–161S.
[5] Kahan BD, Napoli KL, Kelly PA, Podbielski J, Hussein I, Urbauer DL, Katz SH, Van Buren CT.. Therapeutic drug monitoring of sirolimus: correlations with efficacy and toxicity. Clin Transplant 2000; 14: 97-109.
[6] Zochowska D, Bartłomiejczyk I, Kamińska A, Senatorski G, Paczek L. High-performance liquid chromatography versus immunoassay for the measurement of sirolimus: comparison of two methods. Transplant Proc 2006; 38: 78-80.
[7] Kahan BD. Sirolimus: a ten-year perspective. Transplant Proc 2004; 36: 71-5.
[8] Kirchner GI, Jacobsen W, Deters M, Christians U, Nashan B, Winkler M, Vidal C, Kaever V, Sewing K, Manns MP.. Fast quantification method for sirolimus and its major metabolites. Transplant
Proc 2001, 33: 1091-2.
[9] Taylor PJ, Salm P, Lynch SV, Pillans IP. Simultaneous quantification of tacrolimus and sirolimus in human blood, by high-performance liquid chromatography-tandem mass spectrometry. Ther Drug Monit 2000; 22: 608-12.
[10] Buhaescu I, Izzedine H, Covic A. Sirolimuschallenging current perspectives. Ther Drug Monit 2006; 28: 577-84.
[11] Morris RG, Salm P, Taylor PJ, Wicks FA, Theodossi A. Comparison of the reintroduced MEIA assay with HPLC-MS/MS for the determination of whole-blood sirolimus from transplant recipients. Ther Drug Monit 2006; 28:164-8.
[12] Wilson D, Johnston F, Holt D, Moreton M, Engelmayer J, Gaulier JM, Luthe H, Marquet P, Moscato D, Oellerich M, Mosso R, Streit F, Brunet M, Fillee C, Schmid R, Wallemacq P, Barnes G. Multi-center evaluation of analytical performance of the microparticle enzyme immunoassay for sirolimus. Clin Biochem 2006;39: 378-86.
[13] Khoschsorur Gh, Fruehwirth F, Zelzer S, Stettin M, Halwachs-Baumann G. Comparison of fluorescent polarization immunoassay (FPIA) versus HPLC to measure everolimus blood concentrations in clinical transplantation. Clinica Chimica Acta 2007; 380: 217-21.
[14] Wong SHY. Therapeutic drug monitoring for immunosuppressants. Clinica Chimica Acta 2001; 313: 241-53.
[15] Bargnoux AS, Bonardet A, Chong G, Garrigue V, Deleuze S, Dupuy AM, Mourad G, Cristol JP. Evaluation of an immunoassay (Abbott-IMX Analyzer) allowing routine determination of sirolimus: comparison with LC-MS method. Transplant Proc 2006; 38: 2352-3.
[16] Poquette MA, Lensmeyer G L, Doran TC. Effective use of liquid chromatography-mass spectrometry (LC/MS) in the routine clinical laboratory for monitoring sirolimus, tacrolimus, and cyclosporine. Ther Drug Monit 2005; 27: 144-50.
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