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基于验证的药代动力学-药效学模型对华法林的药代动力学进行评估。

Evaluation of pharmacokinetics of warfarin from validated pharmacokinetic-pharmacodynamic model.

作者信息

Sridharan Kannan, Al Banna Rashed, Husain Aysha

机构信息

Department of Pharmacology & Therapeutics, College of Medicine & Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain.

Department of Cardiology, Salmaniya Medical Hospital, Ministry of Health, Manama, Kingdom of Bahrain.

出版信息

ADMET DMPK. 2021 Jan 18;9(2):143-149. doi: 10.5599/admet.909. eCollection 2021.

DOI:10.5599/admet.909
PMID:35299771
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8920105/
Abstract

BACKGROUND

Pharmacokinetics of warfarin has not been described in our population. We derived the pharmacokinetic parameters from a validated pharmacokinetic-pharmacodynamic model.

METHODS

Patients receiving warfarin for at least 6 months were recruited and their demographic characteristics, prothrombin time international normalized ratio (PT-INR), warfarin doses and concomitant drugs were collected. Using a validated pharmacokinetic-pharmacodynamic model, we predicted maximum plasma concentration ( ), total clearance ( ), volume of distribution ( ) and elimination rate (). Warfarin sensitive index (WSI) and warfarin composite measures (WCM) were estimated from the dose and INR values. Liver weight was predicted using validated formula.

RESULTS

Two-hundred and twenty patients were recruited. The following were the predicted pharmacokinetic parameters: (mg/L) was 5.8 (0.4); (L/day) was 1 (0.1); CL (L/day) was 2.1 (0.2); and (L) was 7.6 (0.2). Patients with and elimination rate outside the mean+1.96 SD had significantly lower WSI and higher WCM. Significant correlations were observed between with CL, , and of warfarin. Significant correlations were also observed between CL and of warfarin with liver weight of the study participants.

CONCLUSION

We predicted pharmacokinetic parameters of warfarin from the validated pharmacokinetic-pharmacodynamic model in our population. More studies are needed exploring the relationship between various pharmacodynamic indices of warfarin and pharmacokinetic parameters of warfarin.

摘要

背景

华法林在我们人群中的药代动力学尚未得到描述。我们从一个经过验证的药代动力学-药效学模型中推导了药代动力学参数。

方法

招募接受华法林治疗至少6个月的患者，并收集他们的人口统计学特征、凝血酶原时间国际标准化比值（PT-INR）、华法林剂量和伴随用药情况。使用经过验证的药代动力学-药效学模型，我们预测了最大血浆浓度（）、总清除率（）、分布容积（）和消除率（）。根据剂量和INR值估算华法林敏感指数（WSI）和华法林综合指标（WCM）。使用经过验证的公式预测肝脏重量。

结果

招募了220名患者。预测的药代动力学参数如下：（mg/L）为5.8（0.4）；（L/天）为1（0.1）；CL（L/天）为2.1（0.2）；（L）为7.6（0.2）。最大血浆浓度和消除率超出均值+1.96标准差的患者，其WSI显著较低，WCM较高。观察到华法林的最大血浆浓度与CL、分布容积和消除率之间存在显著相关性。还观察到华法林的CL和分布容积与研究参与者的肝脏重量之间存在显著相关性。

结论

我们从经过验证的药代动力学-药效学模型中预测了我们人群中华法林的药代动力学参数。需要更多研究来探索华法林各种药效学指标与药代动力学参数之间的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9278/8920105/deef5b42ba29/admet-9-909-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9278/8920105/e698bba2b453/admet-9-909-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9278/8920105/b578796d9909/admet-9-909-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9278/8920105/deef5b42ba29/admet-9-909-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9278/8920105/e698bba2b453/admet-9-909-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9278/8920105/b578796d9909/admet-9-909-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9278/8920105/deef5b42ba29/admet-9-909-g003.jpg

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