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PBPK/PD Modeling of Nifedipine for Precision Medicine in Pregnant Women: Enhancing Clinical Decision-Making for Optimal Drug Therapy
Liu, Xinyang1,2; Wang, Wei1; Chen, Jingsi3,4; Chen, Dunjin3,4; Tao, Yong5; Ouyang, Defang1,6
2023-12-04
Source PublicationPharmaceutical Research
ISSN0724-8741
Volume41Issue:1Pages:63-75
Abstract

Objective: This study aims to develop physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) predictive models for nifedipine in pregnant women, enhancing precision medicine and reducing adverse reactions for both mothers and infants. Methods: A PBPK/PD model was constructed using PK-Sim, MoBi, and MATLAB software, integrating literature and pregnancy-specific physiological information. The process involved: (1) establishing and validating a PBPK model for serum clearance after intravenous administration in non-pregnant individuals, (2) establishing and validating a PBPK model for serum clearance after oral administration in non-pregnant individuals, (3) constructing and validating a PBPK model for enzyme clearance after oral administration in non-pregnant individuals, and (4) adjusting the PBPK model structure and enzyme parameters according to pregnant women and validating it in oral administration. (5) PK/PD model was explored through MATLAB, and the PBPK and PK/PD models were integrated to form the PBPK/PD model. Results: The Nifedipine PBPK model's predictive accuracy was confirmed by non-pregnant and pregnant validation studies. The developed PBPK/PD model accurately predicted maximum antihypertensive effects for clinical doses of 5, 10, and 20 mg. The model suggested peak effect at 0.86 h post-administration, achieving blood pressure reductions of 5.4 mmHg, 14.3 mmHg, and 21.3 mmHg, respectively. This model provides guidance for tailored dosing in pregnancy-induced hypertension based on targeted blood pressure reduction. Conclusion: Based on available literature data, the PBPK/PD model of Nifedipine in pregnancy demonstrated good predictive performance. It will help optimize individualized dosing of Nifedipine, improve treatment outcomes, and minimize the risk of adverse reactions in mothers and infants.

KeywordNifedipine Pbpk/pd Precision Medicine Pregnancy
DOI10.1007/s11095-023-03638-2
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaChemistry ; Pharmacology & Pharmacy
WOS SubjectChemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS IDWOS:001120070200001
PublisherSPRINGER/PLENUM PUBLISHERS, 233 SPRING ST, NEW YORK, NY 10013
Scopus ID2-s2.0-85178398759
Fulltext Access
Citation statistics
Document TypeJournal article
CollectionDEPARTMENT OF PUBLIC HEALTH AND MEDICINAL ADMINISTRATION
Institute of Chinese Medical Sciences
THE STATE KEY LABORATORY OF QUALITY RESEARCH IN CHINESE MEDICINE (UNIVERSITY OF MACAU)
Corresponding AuthorOuyang, Defang
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences (ICMS)/FHS, University of Macau, Avenida da Universidade, Taipa, Macao
2.Department of Pharmacy, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China
3.Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China
4.Key Laboratories for Major Obstetric Diseases of Guangdong Province, Guangzhou, 510150, China
5.Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, No. 8, South Road of Worker’s Stadium, Chaoyang District, 100020, China
6.Department of Public Health and Medicinal Administration, Faculty of Health Sciences (FHS), University of Macau, Macao
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences;  Faculty of Health Sciences
Recommended Citation
GB/T 7714
Liu, Xinyang,Wang, Wei,Chen, Jingsi,et al. PBPK/PD Modeling of Nifedipine for Precision Medicine in Pregnant Women: Enhancing Clinical Decision-Making for Optimal Drug Therapy[J]. Pharmaceutical Research, 2023, 41(1), 63-75.
APA Liu, Xinyang., Wang, Wei., Chen, Jingsi., Chen, Dunjin., Tao, Yong., & Ouyang, Defang (2023). PBPK/PD Modeling of Nifedipine for Precision Medicine in Pregnant Women: Enhancing Clinical Decision-Making for Optimal Drug Therapy. Pharmaceutical Research, 41(1), 63-75.
MLA Liu, Xinyang,et al."PBPK/PD Modeling of Nifedipine for Precision Medicine in Pregnant Women: Enhancing Clinical Decision-Making for Optimal Drug Therapy".Pharmaceutical Research 41.1(2023):63-75.
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