关键词:
药品动态学
剂型
cyclosporine
tacrolimus
疗剂监测
肾脏移植
sirolimus
摘要:
Sirolimus (SRL) solution was launched in Taiwan in 2001. It could enhance the effect of cyclosporine (CsA)-based or tacrolimus (FK)-based regimen. SRL, CsA and FK are the most potent immunosuppressants in current use. As a potent immunosuppressant, blood concentration determination is important for SRL. As 95% of the drug partitions in red blood cells, tedious extraction procedure is required. It is unstable at temperature above 25 degree Celsius and light-sensitive. Protected from light is essential in sample handling, storage and analysis. Currently, SRL blood concentrations can be analyzed by high performance liquid chromatography (HPLC) only, which makes routine blood level monitoring difficult. Fix-dose regimen of SRL was therefore recommended by manufacturer. However, clinical trial in National Taiwan University Hospital (NTUH) in 2000 revealed that frequent dosage reduction of the concurrent CsA was necessary. At that time, SRL could not be assayed domestically, and it cost US$ 1000 per sample when assayed abroad. The author therefore set up a SRL lab in NTUH. A new protocol with addition of SRL and reduced dose of CsA or FK based on the original critical pathway was designed. With blood levels of SRL, CsA and FK, as well as ADRs and effectiveness, we could individualize therapy and had better understanding of the pharmacokinetics and posology of *** the help of Wyeth-Ayerst Laboratories, a validated HPLC/UV method developed by them with small modification was set up in NTUH to determine SRL concentration in human whole blood. The accuracy and precision of the SRL assay were validated by Wyeth-Ayerst Laboratories. By reviewing the chemical properties and different HPLC-UV method of SRL, the author wrote an article to share our experience as the first SRL lab in Taiwan using HPLC-UV method, which contributed the keys to *** limitation of quantification was 2.5 ng/mL and the standard curve was linear at the concentration range of 2.5