成人患者地高辛的群体药代动力学及给药方案优化

Population pharmacokinetics and optimization of the dosing regimen of digoxin in adult patients.

作者信息

Komatsu Toshiaki, Morita Mami, Miyaji Futaba, Inomata Takayuki, Ako Junya, Atsuda Koichiro

机构信息

Department of Pharmacy, Kitasato University Hospital, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa 252-0375 Japan.

Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.

出版信息

J Pharm Health Care Sci. 2015 Sep 25;1:25. doi: 10.1186/s40780-015-0023-6. eCollection 2015.

DOI:10.1186/s40780-015-0023-6

PMID:26819736

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4728823/

Abstract

BACKGROUND

This study aimed to evaluate the population pharmacokinetics of digoxin in Japanese patients and establish a dosage regimen based on the pharmacokinetic data.

METHODS

We analyzed 287 serum digoxin samples from 192 individuals by using the nonlinear mixed effects model. We used simulations to optimize the dosage regimen of digoxin to achieve a high likelihood of the target concentration (0.5-0.8 ng/mL).

RESULTS

The total body clearance (CL/F ([L/h]) was calculated using the following formula: CL/F = (1.21 + 0.0532 × CLcr [(mL/min]) × (1 + 0.787 × AMD), where CLcr is the creatinine clearance and AMD is 0 in the case of concomitant administration of amiodarone and 1 otherwise. To achieve the target concentration (0.5-0.8 ng/mL), the dosage of digoxin was 0.0625 mg/day (CLcr < 35 mL/min and AMD = 0); 0.125 mg/day (CLcr, 35-65 mL/min and AMD = 0); 0.1875 mg/day (CLcr, 65-100 mL/min and AMD = 0); 0.0625 mg/every other day (CLcr < 30 mL/min and AMD = 1); and 0.0625 mg/day (CLcr, 30-85 mL/min and AMD = 1).

CONCLUSIONS

Our findings suggest that population parameters are useful for evaluating digoxin pharmacokinetics.

摘要

背景

本研究旨在评估地高辛在日本患者中的群体药代动力学，并根据药代动力学数据制定给药方案。

方法

我们使用非线性混合效应模型分析了192名个体的287份血清地高辛样本。我们通过模拟优化地高辛的给药方案，以提高达到目标浓度（0.5 - 0.8 ng/mL）的可能性。

结果

总体清除率（CL/F [L/h]）使用以下公式计算：CL/F = (1.21 + 0.0532 × CLcr [(mL/min]) × (1 + 0.787 × AMD)，其中CLcr为肌酐清除率，在同时使用胺碘酮时AMD为0，否则为1。为达到目标浓度（0.5 - 0.8 ng/mL），地高辛的剂量为：肌酐清除率<35 mL/min且AMD = 0时，0.0625 mg/天；肌酐清除率为35 - 65 mL/min且AMD = 0时，0.125 mg/天；肌酐清除率为65 - 100 mL/min且AMD = 0时，0.1875 mg/天；肌酐清除率<30 mL/min且AMD = 1时，每隔日0.0625 mg；肌酐清除率为30 - 85 mL/min且AMD = 1时，0.0625 mg/天。