دورية أكاديمية
A population pharmacokinetic study of tacrolimus in healthy Chinese volunteers and liver transplant patients
| العنوان: | A population pharmacokinetic study of tacrolimus in healthy Chinese volunteers and liver transplant patients |
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| المؤلفون: | Lu, Yan-xia, Su, Qing-hong, Wu, Ke-hua, Ren, Yu-peng, Li, Liang, Zhou, Tian-yan, Lu, Wei |
| المساهمون: | Lu, W (reprint author), Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100191, Peoples R China., Gen Hosp Armed Police Forces, Beijing 100039, Peoples R China., Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100191, Peoples R China., Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China. |
| المصدر: | SCI ; PubMed |
| بيانات النشر: | 中国药理学报 |
| سنة النشر: | 2015 |
| المجموعة: | Peking University Institutional Repository (PKU IR) / 北京大学机构知识库 |
| مصطلحات موضوعية: | liver transplantation, healthy volunteer, immunosuppressant, tacrolimus, population pharmacokinetics, serum alanine aminotransferase, PROTEIN-BINDING, HUMAN BLOOD, RECIPIENTS, FK506, IMMUNOSUPPRESSION, PHARMACOGENETICS, EVOLUTION, FK-506, DRUGS |
| الوصف: | Aim: To develop a population pharmacokinetic (PopPK) model of tacrolimus in healthy Chinese volunteers and liver transplant recipients for investigating the difference between the populations, and for potential individualized medication. Methods: A set of 1100 sparse trough concentration data points from 112 orthotopic liver transplant recipients, as well as 851 dense data points from 40 healthy volunteers receiving a single dose of tacrolimus (2 mg, po) were collected. PopPK model of tacrolimus was constructed using the program NONMEM. Related covariates such as age, hepatic and renal functions that were potentially associated with tacrolimus disposition were evaluated. The final model was validated using bootstrapping and a visual predictive check. Results: A two-compartment model of tacrolimus could best describe the data from the two populations. The final model including two covariates, population (liver transplant recipients or volunteers) and serum ALT (alanine aminotransferase) level, was verified and adequately described the pharmacokinetic characteristics of tacrolimus. The estimates of V2/F, Q/F and V3/F were 22.7 L, 76.3 L/h and 916 L, respectively. The estimated CL/F in the volunteers and liver transplant recipients was 32.8 and 18.4 L/h, respectively. Serum ALT level was inversely related to CL/F, whereas age did not influence CL/F. Thus, the elderly (>= 65 years) and adult (<65 years) groups in the liver transplant recipients showed no significant difference in the clearance of tacrolimus. Conclusion: Compared with using the sparse data only, the integrating modeling technique combining sparse data from the patients and dense data from the healthy volunteers improved the PopPK analysis of tacrolimus. ; Chemistry, Multidisciplinary ; Pharmacology & Pharmacy ; SCI(E) ; PubMed ; 中国科技核心期刊(ISTIC) ; 中国科学引文数据库(CSCD) ; 0 ; ARTICLE ; luwei_pk@bjmu.edu.cn ; 2 ; 281-288 ; 36 |
| نوع الوثيقة: | journal/newspaper |
| اللغة: | English |
| تدمد: | 1671-4083 1745-7254 |
| العلاقة: | ACTA PHARMACOLOGICA SINICA.2015,36,(2),281-288.; 651415; http://hdl.handle.net/20.500.11897/322997Test; WOS:000349333700014 |
| DOI: | 10.1038/aps.2014.110 |
| الإتاحة: | https://doi.org/20.500.11897/322997Test https://doi.org/10.1038/aps.2014.110Test https://hdl.handle.net/20.500.11897/322997Test |
| رقم الانضمام: | edsbas.61CAFEDD |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 16714083 17457254 |
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| DOI: | 10.1038/aps.2014.110 |