دورية أكاديمية
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Inter-Species Pharmacokinetic Modeling and Scaling for Drug Repurposing of Pyronaridine and Artesunate.

التفاصيل البيبلوغرافية
العنوان: Inter-Species Pharmacokinetic Modeling and Scaling for Drug Repurposing of Pyronaridine and Artesunate.
المؤلفون: Kang DW; College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Gyeonggi-do, Republic of Korea., Kim JH; College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Gyeonggi-do, Republic of Korea., Kim KM; College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Gyeonggi-do, Republic of Korea., Cho SJ; College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Gyeonggi-do, Republic of Korea., Choi GW; College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Gyeonggi-do, Republic of Korea., Cho HY; College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Gyeonggi-do, Republic of Korea.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2024 Jun 26; Vol. 25 (13). Date of Electronic Publication: 2024 Jun 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Artesunate*/pharmacokinetics , Artesunate*/pharmacology , Drug Repositioning*/methods , Naphthyridines*/pharmacokinetics , Naphthyridines*/pharmacology , Artemisinins*/pharmacokinetics, Animals ; Rats ; Dogs ; Species Specificity ; Humans ; Models, Biological ; Male ; Antimalarials/pharmacokinetics ; Antimalarials/pharmacology
مستخلص: Even though several new targets (mostly viral infection) for drug repurposing of pyronaridine and artesunate have recently emerged in vitro and in vivo, inter-species pharmacokinetic (PK) data that can extend nonclinical efficacy to humans has not been reported over 30 years of usage. Since extrapolation of animal PK data to those of humans is essential to predict clinical outcomes for drug repurposing, this study aimed to investigate inter-species PK differences in three animal species (hamster, rat, and dog) and to support clinical translation of a fixed-dose combination of pyronaridine and artesunate. PK parameters (e.g., steady-state volume of distribution (V ss ), clearance (CL), area under the concentration-time curve (AUC), mean residence time (MRT), etc.) of pyronaridine, artesunate, and dihydroartemisinin (an active metabolite of artesunate) were determined by non-compartmental analysis. In addition, one- or two-compartment PK modeling was performed to support inter-species scaling. The PK models appropriately described the blood concentrations of pyronaridine, artesunate, and dihydroartemisinin in all animal species, and the estimated PK parameters in three species were integrated for inter-species allometric scaling to predict human PKs. The simple allometric equation ( Y = a × W b ) well explained the relationship between PK parameters and the actual body weight of animal species. The results from the study could be used as a basis for drug repurposing and support determining the effective dosage regimen for new indications based on in vitro/in vivo efficacy data and predicted human PKs in initial clinical trials.
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فهرسة مساهمة: Keywords: allometric scaling; artesunate; drug repurposing; inter-species scaling; pharmacokinetics; pyronaridine
المشرفين على المادة: 60W3249T9M (Artesunate)
TD3P7Q3SG6 (pyronaridine)
0 (Naphthyridines)
0 (Artemisinins)
0 (Antimalarials)
تواريخ الأحداث: Date Created: 20240713 Date Completed: 20240713 Latest Revision: 20240715
رمز التحديث: 20240715
مُعرف محوري في PubMed: PMC11241507
DOI: 10.3390/ijms25136998
PMID: 39000107
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms25136998