Adaptation of a population pharmacokinetic model to inform tacrolimus therapy in heart transplant recipients

他克莫司 加药 药代动力学 人口 医学 相伴的 药理学 内科学 移植 环境卫生
作者
Ranita Kirubakaran,David W. Uster,Stefanie Hennig,Jane E. Carland,Richard O. Day,Sebastian G. Wicha,Sophie L. Stocker
出处
期刊:British Journal of Clinical Pharmacology [Wiley]
卷期号:89 (3): 1162-1175 被引量:6
标识
DOI:10.1111/bcp.15566
摘要

Aim Existing tacrolimus population pharmacokinetic models are unsuitable for guiding tacrolimus dosing in heart transplant recipients. This study aimed to develop and evaluate a population pharmacokinetic model for tacrolimus in heart transplant recipients that considers the tacrolimus‐azole antifungal interaction. Methods Data from heart transplant recipients ( n = 87) administered the oral immediate‐release formulation of tacrolimus (Prograf®) were collected. Routine drug monitoring data, principally trough concentrations, were used for model building ( n = 1099). A published tacrolimus model was used to inform the estimation of K a , V 2 /F, Q/F and V 3 /F. The effect of concomitant azole antifungal use on tacrolimus CL/F was quantified. Fat‐free mass was implemented as a covariate on CL/F, V 2 /F, V 3 /F and Q/F on an allometry scale. Subsequently, stepwise covariate modelling was performed. Significant covariates influencing tacrolimus CL/F were included in the final model. Robustness of the final model was confirmed using prediction‐corrected visual predictive check (pcVPC). The final model was externally evaluated for prediction of tacrolimus concentrations of the fourth dosing occasion ( n = 87) from one to three prior dosing occasions. Results Concomitant azole antifungal therapy reduced tacrolimus CL/F by 80%. Haematocrit (∆OFV = −44, P < .001) was included in the final model. The pcVPC of the final model displayed good model adequacy. One recent drug concentration is sufficient for the model to guide tacrolimus dosing. Conclusion A population pharmacokinetic model that adequately describes tacrolimus pharmacokinetics in heart transplant recipients, considering the tacrolimus–azole antifungal interaction was developed. Prospective evaluation is required to assess its clinical utility to improve patient outcomes.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
隐形曼青应助顺利鹤采纳,获得10
刚刚
haihuhu完成签到 ,获得积分10
刚刚
HZY发布了新的文献求助10
刚刚
1秒前
1秒前
1秒前
1秒前
小超人完成签到,获得积分20
1秒前
LSY完成签到,获得积分10
2秒前
abby123完成签到,获得积分10
2秒前
2秒前
choi发布了新的文献求助10
2秒前
卓梨完成签到 ,获得积分10
3秒前
taco完成签到,获得积分10
3秒前
烟花应助zhangtengteng采纳,获得10
3秒前
妮妮完成签到,获得积分10
3秒前
sota完成签到,获得积分10
4秒前
含蓄心锁完成签到,获得积分10
4秒前
4秒前
4秒前
123完成签到,获得积分10
4秒前
科目三应助馨馨采纳,获得10
5秒前
科研通AI2S应助MosesXie采纳,获得10
5秒前
一点不懂发布了新的文献求助10
5秒前
和谐的寄凡完成签到,获得积分10
5秒前
6秒前
无奈敏完成签到,获得积分10
6秒前
6秒前
djbj2022发布了新的文献求助80
7秒前
7秒前
Isaac完成签到,获得积分10
7秒前
弥秋完成签到,获得积分10
8秒前
欣慰小丸子完成签到,获得积分10
8秒前
向日葵完成签到,获得积分10
8秒前
务实的鸽子完成签到,获得积分10
8秒前
leon发布了新的文献求助10
8秒前
仂尤发布了新的文献求助10
9秒前
zzcres完成签到,获得积分10
9秒前
小海完成签到,获得积分10
10秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3969060
求助须知:如何正确求助?哪些是违规求助? 3513962
关于积分的说明 11171223
捐赠科研通 3249302
什么是DOI,文献DOI怎么找? 1794772
邀请新用户注册赠送积分活动 875377
科研通“疑难数据库(出版商)”最低求助积分说明 804769