Pharmacokinetic Evaluation of Tacrolimus in Chinese Adult Patients during the Early Stages Post-Lung Transplantation

Although tacrolimus has been widely used in patients undergoing lung transplantation, few studies have reported the pharmacokinetics of tacrolimus in Chinese patients after lung transplantation. Thus, we aimed to investigate the pharmacokinetics and influential factors in this patient cohort in the...

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Published inJournal of personalized medicine Vol. 13; no. 4; p. 656
Main Authors Cui, Yi-Fan, Pan, Yan, Zhu, Min-Fang, Jiao, Zheng
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 11.04.2023
MDPI
Subjects
Analysis
Cystic fibrosis
Drug dosages
Enzymes
Ethylenediaminetetraacetic acid
Gene polymorphism
Genetic polymorphisms
Immunotherapy
Lung transplantation
Lung transplants
Mycophenolate mofetil
Patients
Pharmacokinetics
Population
Precision medicine
Steroids
Surgery
Tacrolimus
Transplantation of organs, tissues, etc
White people
China
Belgium
United States > US
Ireland
Chinese population
pharmacokinetics
lung transplantation
tacrolimus
CYP3A4/5 enzyme
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Abstract Although tacrolimus has been widely used in patients undergoing lung transplantation, few studies have reported the pharmacokinetics of tacrolimus in Chinese patients after lung transplantation. Thus, we aimed to investigate the pharmacokinetics and influential factors in this patient cohort in the early stage after lung transplantation. We enrolled 14 adult lung transplant recipients who were treated with tacrolimus and then intensively collected blood samples within a 12-h dosing interval. The pharmacokinetic parameters of tacrolimus were calculated using non-compartmental analysis, and the influence of pathophysiological characteristics and CYP3A5*3 and CYP3A4*1G genotypes on the pharmacokinetics of tacrolimus was assessed. Using linear regression analysis, we investigated the correlation between tacrolimus concentration at different sampling points and measured the area under the time-concentration curve (AUC ). Geometric mean of apparent clearance (CL/F) was 18.13 ± 1.65 L/h in non-CYP3A5*3/*3 carriers, five times higher than that in CYP3A5*3/*3 carriers ( < 0.001). Furthermore, the tacrolimus concentration 4 h after administration had the strongest correlation with AUC (R = 0.979). The pharmacokinetics of tacrolimus varied largely between patients during the early stage post-transplantation, which could be partially explained by CYP3A5*3 genetic polymorphisms.
AbstractList Although tacrolimus has been widely used in patients undergoing lung transplantation, few studies have reported the pharmacokinetics of tacrolimus in Chinese patients after lung transplantation. Thus, we aimed to investigate the pharmacokinetics and influential factors in this patient cohort in the early stage after lung transplantation. We enrolled 14 adult lung transplant recipients who were treated with tacrolimus and then intensively collected blood samples within a 12-h dosing interval. The pharmacokinetic parameters of tacrolimus were calculated using non-compartmental analysis, and the influence of pathophysiological characteristics and CYP3A5*3 and CYP3A4*1G genotypes on the pharmacokinetics of tacrolimus was assessed. Using linear regression analysis, we investigated the correlation between tacrolimus concentration at different sampling points and measured the area under the time-concentration curve (AUC ). Geometric mean of apparent clearance (CL/F) was 18.13 ± 1.65 L/h in non-CYP3A5*3/*3 carriers, five times higher than that in CYP3A5*3/*3 carriers ( < 0.001). Furthermore, the tacrolimus concentration 4 h after administration had the strongest correlation with AUC (R = 0.979). The pharmacokinetics of tacrolimus varied largely between patients during the early stage post-transplantation, which could be partially explained by CYP3A5*3 genetic polymorphisms.
Background: Although tacrolimus has been widely used in patients undergoing lung transplantation, few studies have reported the pharmacokinetics of tacrolimus in Chinese patients after lung transplantation. Thus, we aimed to investigate the pharmacokinetics and influential factors in this patient cohort in the early stage after lung transplantation. Methods: We enrolled 14 adult lung transplant recipients who were treated with tacrolimus and then intensively collected blood samples within a 12-h dosing interval. The pharmacokinetic parameters of tacrolimus were calculated using non-compartmental analysis, and the influence of pathophysiological characteristics and CYP3A5*3 and CYP3A4*1G genotypes on the pharmacokinetics of tacrolimus was assessed. Using linear regression analysis, we investigated the correlation between tacrolimus concentration at different sampling points and measured the area under the time-concentration curve (AUC0–12h). Results: Geometric mean of apparent clearance (CL/F) was 18.13 ± 1.65 L/h in non-CYP3A5*3/*3 carriers, five times higher than that in CYP3A5*3/*3 carriers (p < 0.001). Furthermore, the tacrolimus concentration 4 h after administration had the strongest correlation with AUC0–12h (R2 = 0.979). Conclusion: The pharmacokinetics of tacrolimus varied largely between patients during the early stage post-transplantation, which could be partially explained by CYP3A5*3 genetic polymorphisms.
Background: Although tacrolimus has been widely used in patients undergoing lung transplantation, few studies have reported the pharmacokinetics of tacrolimus in Chinese patients after lung transplantation. Thus, we aimed to investigate the pharmacokinetics and influential factors in this patient cohort in the early stage after lung transplantation. Methods: We enrolled 14 adult lung transplant recipients who were treated with tacrolimus and then intensively collected blood samples within a 12-h dosing interval. The pharmacokinetic parameters of tacrolimus were calculated using non-compartmental analysis, and the influence of pathophysiological characteristics and CYP3A5*3 and CYP3A4*1G genotypes on the pharmacokinetics of tacrolimus was assessed. Using linear regression analysis, we investigated the correlation between tacrolimus concentration at different sampling points and measured the area under the time-concentration curve (AUC 0–12h ). Results: Geometric mean of apparent clearance (CL/F) was 18.13 ± 1.65 L/h in non-CYP3A5*3/*3 carriers, five times higher than that in CYP3A5*3/*3 carriers ( p < 0.001). Furthermore, the tacrolimus concentration 4 h after administration had the strongest correlation with AUC 0–12h (R 2 = 0.979). Conclusion: The pharmacokinetics of tacrolimus varied largely between patients during the early stage post-transplantation, which could be partially explained by CYP3A5*3 genetic polymorphisms.
Background: Although tacrolimus has been widely used in patients undergoing lung transplantation, few studies have reported the pharmacokinetics of tacrolimus in Chinese patients after lung transplantation. Thus, we aimed to investigate the pharmacokinetics and influential factors in this patient cohort in the early stage after lung transplantation. Methods: We enrolled 14 adult lung transplant recipients who were treated with tacrolimus and then intensively collected blood samples within a 12-h dosing interval. The pharmacokinetic parameters of tacrolimus were calculated using non-compartmental analysis, and the influence of pathophysiological characteristics and CYP3A5*3 and CYP3A4*1G genotypes on the pharmacokinetics of tacrolimus was assessed. Using linear regression analysis, we investigated the correlation between tacrolimus concentration at different sampling points and measured the area under the time-concentration curve (AUC[sub.0-12h]). Results: Geometric mean of apparent clearance (CL/F) was 18.13 ± 1.65 L/h in non-CYP3A5*3/*3 carriers, five times higher than that in CYP3A5*3/*3 carriers (p < 0.001). Furthermore, the tacrolimus concentration 4 h after administration had the strongest correlation with AUC[sub.0-12h] (R[sup.2] = 0.979). Conclusion: The pharmacokinetics of tacrolimus varied largely between patients during the early stage post-transplantation, which could be partially explained by CYP3A5*3 genetic polymorphisms.
BACKGROUNDAlthough tacrolimus has been widely used in patients undergoing lung transplantation, few studies have reported the pharmacokinetics of tacrolimus in Chinese patients after lung transplantation. Thus, we aimed to investigate the pharmacokinetics and influential factors in this patient cohort in the early stage after lung transplantation. METHODSWe enrolled 14 adult lung transplant recipients who were treated with tacrolimus and then intensively collected blood samples within a 12-h dosing interval. The pharmacokinetic parameters of tacrolimus were calculated using non-compartmental analysis, and the influence of pathophysiological characteristics and CYP3A5*3 and CYP3A4*1G genotypes on the pharmacokinetics of tacrolimus was assessed. Using linear regression analysis, we investigated the correlation between tacrolimus concentration at different sampling points and measured the area under the time-concentration curve (AUC0-12h). RESULTSGeometric mean of apparent clearance (CL/F) was 18.13 ± 1.65 L/h in non-CYP3A5*3/*3 carriers, five times higher than that in CYP3A5*3/*3 carriers (p < 0.001). Furthermore, the tacrolimus concentration 4 h after administration had the strongest correlation with AUC0-12h (R2 = 0.979). CONCLUSIONThe pharmacokinetics of tacrolimus varied largely between patients during the early stage post-transplantation, which could be partially explained by CYP3A5*3 genetic polymorphisms.
Audience Academic
Author Jiao, Zheng
Cui, Yi-Fan
Zhu, Min-Fang
Pan, Yan
AuthorAffiliation 1 Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
2 School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China
3 Department of Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
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Issue 4
Keywords Chinese population
pharmacokinetics
lung transplantation
tacrolimus
CYP3A4/5 enzyme
Language English
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Snippet Although tacrolimus has been widely used in patients undergoing lung transplantation, few studies have reported the pharmacokinetics of tacrolimus in Chinese...
Background: Although tacrolimus has been widely used in patients undergoing lung transplantation, few studies have reported the pharmacokinetics of tacrolimus...
BACKGROUNDAlthough tacrolimus has been widely used in patients undergoing lung transplantation, few studies have reported the pharmacokinetics of tacrolimus in...
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StartPage 656
SubjectTerms Analysis
Cystic fibrosis
Drug dosages
Enzymes
Ethylenediaminetetraacetic acid
Gene polymorphism
Genetic polymorphisms
Immunotherapy
Lung transplantation
Lung transplants
Mycophenolate mofetil
Patients
Pharmacokinetics
Population
Precision medicine
Steroids
Surgery
Tacrolimus
Transplantation of organs, tissues, etc
White people
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Title Pharmacokinetic Evaluation of Tacrolimus in Chinese Adult Patients during the Early Stages Post-Lung Transplantation
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Volume 13
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