Приказ основних података о документу

dc.creatorShi, Changzhi
dc.creatorIgnjatović, Jelisaveta
dc.creatorWang, Junwei
dc.creatorGuo, Yi
dc.creatorZhang, Li
dc.creatorCvijić, Sandra
dc.creatorCun, Dongmei
dc.creatorYang, Mingshi
dc.date.accessioned2022-10-25T08:30:20Z
dc.date.available2022-10-25T08:30:20Z
dc.date.issued2023
dc.identifier.issn1001-8417
dc.identifier.urihttps://farfar.pharmacy.bg.ac.rs/handle/123456789/4291
dc.description.abstractRespiratory antibiotics have been proven clinically beneficial for the treatment of severe lung infections such as Pseudomonas aeruginosa. Maintaining a high local concentration of inhaled antibiotics for an extended time in the lung is crucial to ensure an adequate antimicrobial efficiency. In this study, we aim to investigate whether an extended exposure of ciprofloxacin (CIP), a model fluoroquinolone drug, in the lung epithelial lining fluid (ELF) could be achieved via a controlled-release formulation strategy. CIP solutions were intratracheally instilled to the rat lungs at 3 different rates, i.e., T0h (fast), T2h (medium), and T4h (slow), to mimic different release profiles of inhaled CIP formulations in the lung. Subsequently, the concentration-time profiles of CIP in the plasma and the lung ELF were obtained, respectively, to determine topical exposure index (ELF-Plasma AUC Ratio, EPR). The in silico PBPK model, validated based on the in vivo data, was used to identify the key factors that influence the disposition of CIP in the plasma and lungs. The medium and slow rates groups exhibited much higher EPR than that fast instillation group. The ELF AUC of the medium and slow instillation groups were about 200 times higher than their plasma AUC. In contrast, the ELF AUC of the fast instillation group was only about 20 times higher than the plasma AUC. The generated whole-body PBPK rat model, validated by comparison with the in vivo data, revealed that drug pulmonary absorption rate was the key factor that determined pulmonary absorption of CIP. This study suggests that controlled CIP release from inhaled formulations may extend the exposure of CIP in the ELF post pulmonary administration. It also demonstrates that combining the proposed intratracheal installation model and in silico PBPK model is a useful approach to identify the key factors that influence the absorption and disposition of inhaled medicine.
dc.publisherElsevier B.V.
dc.relationThe Liaoning Pan Deng Xue Zhe Scholar (No. XLYC2002061)
dc.relationThe National Natural Sci- ence Foundation of China (No. 81573380)
dc.relationThe Overseas Exper- tise Introduction Project for Discipline Innovation (“111 Project”) (No. D20029)
dc.relationThe Guiding Project for Science and Technology of Liaoning Province (No. 2019-ZD-0448)
dc.relationMinistry of Education Chunhui Program (2020)
dc.relationinfo:eu-repo/grantAgreement/MESTD/inst-2020/200161/RS//
dc.rightsrestrictedAccess
dc.sourceChinese Chemical Letters
dc.subjectCiprofloxacin
dc.subjectControlled release
dc.subjectInhalation antibiotics
dc.subjectLung infections
dc.subjectPBPK modeling
dc.titleEvaluating the pharmacokinetics of intrapulmonary administered ciprofloxacin solution for respiratory infections using in vivo and in silico PBPK rat model studies
dc.typearticle
dc.rights.licenseARR
dc.citation.volume34
dc.citation.issue1
dc.citation.rankM21~
dc.identifier.wos000875627800001
dc.identifier.doi10.1016/j.cclet.2022.04.061
dc.identifier.scopus2-s2.0-85139728347
dc.type.versionpublishedVersion


Документи

Thumbnail

Овај документ се појављује у следећим колекцијама

Приказ основних података о документу