เภสัชจลนศาสตร์ของยาไซโรลิมุสของอาสาสมัครสุขภาพดีที่มีการทำงานของไตปกติในคนไทย

• Main Author: อัษฎาศ์ ลีฬหวนิชกุล
• Other Authors: เกื้อเกียรติ ประดิษฐ์พรศิลป์
• Format: Theses and Dissertations
• Language: Thai
• Published: จุฬาลงกรณ์มหาวิทยาลัย 2003
• Subjects: เภสัชจลนศาสตร์; ไซโรลิมุส
• Online Access: https://digiverse.chula.ac.th/Info/item/dc:30546
• Institution: Chulalongkorn University

BACKGROUND : Sirolimus , an novel immunosuppressive drug , has been used in kidney transplant recipients to minimize calcineurin inhibitor(CNI) and steroid toxicities. Likewise CNI , Sirolimus s pharmacokinetics vary both inter and intra-individual . Due to ethnic difference, the recommended 6 mg loading dose and 2 mg/day maintenance dose for caucasian 10 mg loading dose and 5 mg/day maintenance dose for African - American recipient may not be appropriate for Asian recipient.Moreover, studies have demonstrated the correlation of drug toxicity and drug exposure .We therefore conducted the pharmacokinetic study of Sirolimus in Thai population and aimed to delineate the appropriate Sirolimus dose for further clinical use.OBJECTIVE :To study pharmacokinetics of Thai Healthy vounteers receiving Sirolimus at the dose of 6 mg. METHODS : The study was performed in 15 Thai healthy volunteers. After an over night fasting , a single oral dose of 6 mg Sirolimus was given. Whole blood concentration of Sirolimus determined by UV high - performance liquid chromatography(HPLC-UV) ,were measured and followed during 0 hour(Co) and 24 hours (C24) after drug administration. The complete pharmacokinetic study was done by using the whole blood Sirolimus level at C0,C0.5,C1,C1.5,C2,C2.5,C3,C4,C6,C8,C12,C24 apply for pharmacokinetic formulation.A complete area under the concentration time curve(AUC) from 0-24hours, AUC0-24hr , was calculated by using the trapezoidal rule. RESULTS : The mean(+-SD) time to maximal concentration (T[subscriptmax]) were 1.45+-0.5 hr (range 1- 3hr).The maximal (C[subscript max]) and minimal plasma concentration (C[subscript trough]) for sirolimus were 25.3 + 6.1ng/ml (range 18.10 - 40 ng/ml)and 4.47?0.57 ng/ml (range 2.90 - 7.20 )ng/ml respectively.The AUC 0-24hr were 187.9 + 48.2ng/ml*hr ( range 151.3 -294.8 ng/ml*hr )Sirolimus level at 4 hr post-dose had the best of correlation with AUC0-24hr (pearson correlation = 0.76,p <0.007).Also,Sirolimus at 24 hour post-dose correlated with AUC[subscript 0-24hr] at peason correlation value of 0.72(p<0.011).One volunteer sirolimus level extreme out of therapeutic range.This subject pharmacokinetic data showed AUC 0-24hr 256 ng/ml*hr and Cmax of 40 ng/ml.but normal range Cmin CONCLUSION : 1. The loading dose of 6 mg sirolimus in Thai volunteers showed C[subscript max],T[sunscript max] and Cmin in lower than previous study in Western population. 2. The loading dose of 6 mg Sirolimus in Thai volunteers do not achieved recommended therapeutic level (5-10 ng/ml) in most subjects . 3. There is 1 subject in Thai study who had extremely high sirolimus level. 4. none of subject in Thai study had any adverse effect of drug.