Developmental Pharmacogenetics of SLCO2B1 on Montelukast Pharmacokinetics in Chinese Children
Qian Li,1,2,* Kai Wang,3,* Hai-Yan Shi,2 Yue-E Wu,1 Yue Zhou,1 Min Kan,1 Yi Zheng,1 Guo-Xiang Hao,1 Xin-Mei Yang,2 Yi-Lei Yang,2 Le-Qun Su,2 Xiao-Ling Wang,4 Evelyne Jacqz-Aigrain,5,6 Jun Zhou,7,* Wei Zhao1,2,* 1Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University,...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2019-12-01
|
| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/developmental-pharmacogenetics-of-slco2b1-on-montelukast-pharmacokinet-peer-reviewed-article-DDDT |
| _version_ | 1818190250689691648 |
|---|---|
| author | Li Q Wang K Shi HY Wu YE Zhou Y Kan M Zheng Y Hao GX Yang XM Yang YL Su LQ Wang XL Jacqz-Aigrain E Zhou J Zhao W |
| author_facet | Li Q Wang K Shi HY Wu YE Zhou Y Kan M Zheng Y Hao GX Yang XM Yang YL Su LQ Wang XL Jacqz-Aigrain E Zhou J Zhao W |
| author_sort | Li Q |
| collection | DOAJ |
| description | Qian Li,1,2,* Kai Wang,3,* Hai-Yan Shi,2 Yue-E Wu,1 Yue Zhou,1 Min Kan,1 Yi Zheng,1 Guo-Xiang Hao,1 Xin-Mei Yang,2 Yi-Lei Yang,2 Le-Qun Su,2 Xiao-Ling Wang,4 Evelyne Jacqz-Aigrain,5,6 Jun Zhou,7,* Wei Zhao1,2,* 1Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, Jinan, People’s Republic of China; 2Department of Pharmacy, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Respiratory Disease, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, People’s Republic of China; 4Clinical Research Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 5Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, AP-HP, Paris, France; 6University Paris Diderot, Sorbonne Paris-Cité, Paris, France; 7Clinical Training Center, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun ZhouClinical Training Center, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, 16766 Jing Shi Street, Jinan 250014, People’s Republic of ChinaTel/Fax +86 531 8237 3200Email zhoujun_jn@163.comWei ZhaoDepartment of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, 44 Culture West Road, Jinan 250012, People’s Republic of ChinaTel/Fax +86 531 8838 3308Email zhao4wei@hotmail.comBackground: Montelukast, a potent oral selective leukotriene-receptor antagonist, inhibits the action of cysteinyl-leukotriene in patients with asthma. Although pharmacokinetic studies of montelukast have been reported in Caucasian adults and children, and showed large inter-individual variability on pharmacokinetics, none of these studies has been explored in Chinese children. Given the potential inter-ethnic difference, the purpose of the present study was to evaluate the effects of developmental factors and pharmacogenetics of CYP2C8 and SLCO2B1 on montelukast clearance in Chinese pediatric patients.Methods: After the administration of montelukast, blood samples were collected from children and plasma concentrations were determined using an adapted micro high-performance liquid chromatography coupled with the fluorescence detection (HPLC-FLD) method. A previously published pharmacokinetic model was validated using the opportunistic pharmacokinetic samples, and individual patient’s clearance was calculated using the validated model. Population pharmacokinetic analysis was performed using a nonlinear mixed-effects model approach (NONMEM V 7.2.0) and variants of CYP2C8 and SLCO2B1 were genotyped.Results: Fifty patients (age range: 0.7–10.0 years) with asthma were enrolled in this study. The clearance of montelukast was significantly higher in children with the SLCO2B1 c.935GA and c.935AA genotypes compared with that of children with the SLCO2B1 c.935GG genotype (0.94 ± 0.26 versus 0.77 ± 0.21, p = 0.020). The patient’s weight was also found to be significantly corrected with montelukast clearance (p <0.0001).Conclusion: The developmental pharmacology of montelukast in Chinese children was evaluated. Weight and SLCO2B1 genotype were found to have independent significant impacts on the clearance of montelukast.Keywords: montelukast, ontogeny, pharmacogenetics, children |
| first_indexed | 2024-12-11T23:55:44Z |
| format | Article |
| id | doaj.art-4d37d51b72eb4fac9b4386deb46fb920 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-11T23:55:44Z |
| publishDate | 2019-12-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-4d37d51b72eb4fac9b4386deb46fb9202022-12-22T00:45:22ZengDove Medical PressDrug Design, Development and Therapy1177-88812019-12-01Volume 134405441150744Developmental Pharmacogenetics of SLCO2B1 on Montelukast Pharmacokinetics in Chinese ChildrenLi QWang KShi HYWu YEZhou YKan MZheng YHao GXYang XMYang YLSu LQWang XLJacqz-Aigrain EZhou JZhao WQian Li,1,2,* Kai Wang,3,* Hai-Yan Shi,2 Yue-E Wu,1 Yue Zhou,1 Min Kan,1 Yi Zheng,1 Guo-Xiang Hao,1 Xin-Mei Yang,2 Yi-Lei Yang,2 Le-Qun Su,2 Xiao-Ling Wang,4 Evelyne Jacqz-Aigrain,5,6 Jun Zhou,7,* Wei Zhao1,2,* 1Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, Jinan, People’s Republic of China; 2Department of Pharmacy, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Respiratory Disease, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, People’s Republic of China; 4Clinical Research Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 5Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, AP-HP, Paris, France; 6University Paris Diderot, Sorbonne Paris-Cité, Paris, France; 7Clinical Training Center, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun ZhouClinical Training Center, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, 16766 Jing Shi Street, Jinan 250014, People’s Republic of ChinaTel/Fax +86 531 8237 3200Email zhoujun_jn@163.comWei ZhaoDepartment of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, 44 Culture West Road, Jinan 250012, People’s Republic of ChinaTel/Fax +86 531 8838 3308Email zhao4wei@hotmail.comBackground: Montelukast, a potent oral selective leukotriene-receptor antagonist, inhibits the action of cysteinyl-leukotriene in patients with asthma. Although pharmacokinetic studies of montelukast have been reported in Caucasian adults and children, and showed large inter-individual variability on pharmacokinetics, none of these studies has been explored in Chinese children. Given the potential inter-ethnic difference, the purpose of the present study was to evaluate the effects of developmental factors and pharmacogenetics of CYP2C8 and SLCO2B1 on montelukast clearance in Chinese pediatric patients.Methods: After the administration of montelukast, blood samples were collected from children and plasma concentrations were determined using an adapted micro high-performance liquid chromatography coupled with the fluorescence detection (HPLC-FLD) method. A previously published pharmacokinetic model was validated using the opportunistic pharmacokinetic samples, and individual patient’s clearance was calculated using the validated model. Population pharmacokinetic analysis was performed using a nonlinear mixed-effects model approach (NONMEM V 7.2.0) and variants of CYP2C8 and SLCO2B1 were genotyped.Results: Fifty patients (age range: 0.7–10.0 years) with asthma were enrolled in this study. The clearance of montelukast was significantly higher in children with the SLCO2B1 c.935GA and c.935AA genotypes compared with that of children with the SLCO2B1 c.935GG genotype (0.94 ± 0.26 versus 0.77 ± 0.21, p = 0.020). The patient’s weight was also found to be significantly corrected with montelukast clearance (p <0.0001).Conclusion: The developmental pharmacology of montelukast in Chinese children was evaluated. Weight and SLCO2B1 genotype were found to have independent significant impacts on the clearance of montelukast.Keywords: montelukast, ontogeny, pharmacogenetics, childrenhttps://www.dovepress.com/developmental-pharmacogenetics-of-slco2b1-on-montelukast-pharmacokinet-peer-reviewed-article-DDDTmontelukastontogenypharmacogeneticschildren |
| spellingShingle | Li Q Wang K Shi HY Wu YE Zhou Y Kan M Zheng Y Hao GX Yang XM Yang YL Su LQ Wang XL Jacqz-Aigrain E Zhou J Zhao W Developmental Pharmacogenetics of SLCO2B1 on Montelukast Pharmacokinetics in Chinese Children Drug Design, Development and Therapy montelukast ontogeny pharmacogenetics children |
| title | Developmental Pharmacogenetics of SLCO2B1 on Montelukast Pharmacokinetics in Chinese Children |
| title_full | Developmental Pharmacogenetics of SLCO2B1 on Montelukast Pharmacokinetics in Chinese Children |
| title_fullStr | Developmental Pharmacogenetics of SLCO2B1 on Montelukast Pharmacokinetics in Chinese Children |
| title_full_unstemmed | Developmental Pharmacogenetics of SLCO2B1 on Montelukast Pharmacokinetics in Chinese Children |
| title_short | Developmental Pharmacogenetics of SLCO2B1 on Montelukast Pharmacokinetics in Chinese Children |
| title_sort | developmental pharmacogenetics of slco2b1 on montelukast pharmacokinetics in chinese children |
| topic | montelukast ontogeny pharmacogenetics children |
| url | https://www.dovepress.com/developmental-pharmacogenetics-of-slco2b1-on-montelukast-pharmacokinet-peer-reviewed-article-DDDT |
| work_keys_str_mv | AT liq developmentalpharmacogeneticsofslco2b1onmontelukastpharmacokineticsinchinesechildren AT wangk developmentalpharmacogeneticsofslco2b1onmontelukastpharmacokineticsinchinesechildren AT shihy developmentalpharmacogeneticsofslco2b1onmontelukastpharmacokineticsinchinesechildren AT wuye developmentalpharmacogeneticsofslco2b1onmontelukastpharmacokineticsinchinesechildren AT zhouy developmentalpharmacogeneticsofslco2b1onmontelukastpharmacokineticsinchinesechildren AT kanm developmentalpharmacogeneticsofslco2b1onmontelukastpharmacokineticsinchinesechildren AT zhengy developmentalpharmacogeneticsofslco2b1onmontelukastpharmacokineticsinchinesechildren AT haogx developmentalpharmacogeneticsofslco2b1onmontelukastpharmacokineticsinchinesechildren AT yangxm developmentalpharmacogeneticsofslco2b1onmontelukastpharmacokineticsinchinesechildren AT yangyl developmentalpharmacogeneticsofslco2b1onmontelukastpharmacokineticsinchinesechildren AT sulq developmentalpharmacogeneticsofslco2b1onmontelukastpharmacokineticsinchinesechildren AT wangxl developmentalpharmacogeneticsofslco2b1onmontelukastpharmacokineticsinchinesechildren AT jacqzaigraine developmentalpharmacogeneticsofslco2b1onmontelukastpharmacokineticsinchinesechildren AT zhouj developmentalpharmacogeneticsofslco2b1onmontelukastpharmacokineticsinchinesechildren AT zhaow developmentalpharmacogeneticsofslco2b1onmontelukastpharmacokineticsinchinesechildren |