Development of a population pharmacokinetic model of pyrazinamide to guide personalized therapy: impacts of geriatric and diabetes mellitus on clearance

被引：7

作者：

Kim, Ryunha ^{[1
,2
]}

Jayanti, Rannissa Puspita ^{[1
,2
]}

Lee, Hongyeul ^{[3
]}

Kim, Hyun-Kuk ^{[4
]}

Kang, Jiyeon ^{[5
]}

Park, I-Nae ^{[6
]}

Kim, Jehun ^{[7
]}

Oh, Jee Youn ^{[8
]}

Kim, Hyung Woo ^{[9
]}

Lee, Heayon ^{[10
]}

Ghim, Jong-Lyul ^{[1
,2
]}

Ahn, Sangzin ^{[1
,2
]}

Long, Nguyen Phuoc ^{[1
,2
]}

Cho, Yong-Soon ^{[1
,2
]}

Shin, Jae-Gook ^{[1
,2
,11
]}

cPMTb

机构：

[1] Inje Univ, Ctr Personalized Precis Med TB, Coll Med, Busan, South Korea

[2] Inje Univ, PharmacoGen Res Ctr, Dept Pharmacol, Coll Med, Busan, South Korea

[3] Inje Univ, Busan Paik Hosp, Dept Internal Med, Div Pulm Crit Care Med,Coll Med, Busan, South Korea

[4] Inje Univ, Dept Internal Med, Div Pulmonol, Haeundae Paik Hosp, Busan, South Korea

[5] Inje Univ, Dept Internal Med, Div Pulm & Crit Care Med, Ilsan Paik Hosp, Goyang, South Korea

[6] Inje Univ, Seoul Paik Hosp, Dept Internal Med, Coll Med, Seoul, South Korea

[7] Kosin Univ, Dept IM, Pulm Div, Gospel Hosp, Busan, South Korea

[8] Korea Univ, Dept Internal Med, Div Pulmonol, Guro Hosp, Seoul, South Korea

[9] Catholic Univ Korea, Incheon St Marys Hosp, Coll Med, Div Pulm & Crit Care Med,Dept Internal Med, Incheon, South Korea

[10] Catholic Univ Korea, Eunpyeong St Marys Hosp, Coll Med, Dept Internal Med,Div Pulm Crit Care & Sleep Med, Seoul, South Korea

[11] Inje Univ, Dept Clin Pharmacol, Busan Paik Hosp, Busan, South Korea

来源：

FRONTIERS IN PHARMACOLOGY | 2023年 / 14卷

基金：

新加坡国家研究基金会;

关键词：

pyrazinamide; tuberculosis; geriatric; diabetes mellitus; population pharmacokinetics; therapeutic drug monitoring; P-GLYCOPROTEIN EXPRESSION; ANTITUBERCULOSIS DRUGS; PULMONARY TUBERCULOSIS; XANTHINE-OXIDASE; TREATMENT RESPONSE; RIFAMPIN; ETHAMBUTOL; EXPOSURE; CHILDREN; AGE;

D O I：

10.3389/fphar.2023.1116226

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

OObjectives: This study was performed to develop a population pharmacokinetic model of pyrazinamide for Korean tuberculosis (TB) patients and to explore and identify the influence of demographic and clinical factors, especially geriatric diabetes mellitus (DM), on the pharmacokinetics (PK) of pyrazinamide (PZA). Methods: PZA concentrations at random post-dose points, demographic characteristics, and clinical information were collected in a multicenter prospective TB cohort study from 18 hospitals in Korea. Data obtained from 610 TB patients were divided into training and test datasets at a 4:1 ratio. A population PK model was developed using a nonlinear mixed-effects method. Results: A one-compartment model with allometric scaling for body size effect adequately described the PK of PZA. Geriatric patients with DM (age >70 years) were identified as a significant covariate, increasing the apparent clearance of PZA by 30% (geriatric patients with DM: 5.73 L/h; others: 4.50 L/h), thereby decreasing the area under the concentration-time curve from 0 to 24 h by a similar degree compared with other patients (geriatric patients with DM: 99.87 mu g h/mL; others: 132.3 mu g h/mL). Our model was externally evaluated using the test set and provided better predictive performance compared with the previously published model. Conclusion: The established population PK model sufficiently described the PK of PZA in Korean TB patients. Our model will be useful in therapeutic drug monitoring to provide dose optimization of PZA, particularly for geriatric patients with DM and TB.

引用

页数：13

共 76 条

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