Calculation of a First-In-Man Dose of 7-O-Succinyl Macrolactin A Based on Allometric Scaling of Data from Mice, Rats, and Dogs
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Noh, Keumhan | - |
dc.contributor.author | Kang, Wonku | - |
dc.date.available | 2019-03-08T07:38:04Z | - |
dc.date.issued | 2017-11 | - |
dc.identifier.issn | 1976-9148 | - |
dc.identifier.issn | 2005-4483 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/3717 | - |
dc.description.abstract | 7-O-Succinyl macrolactin A )SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anticancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice. Pharmacokinetic parameters were estimated via both noncompartmental and compartmental analysis, and were correlated with body weight and/or the potential maximum life-span. The clearance and distribution volume of SMA in humans were predicted, and a first-in-man dose proposed. A two-compartment model best described the time courses of SMA plasma concentrations after a saturation elimination process was applied to fit the dataset obtained from rats. Incorporation of the maximum potential life-span during allometric scaling was required to improve the estimation of human clearance. The SMA clearance and the distribution volume in the steady state, in a 70-kg adult male, were estimated to be 30.6 L/h and 19.5 L, respectively. To meet the area under the curve )AUC) required for anti-tumour activity, a dose of 100 mg (similar to 1.5 mg/kg) was finally proposed as the first dose for a 70-kg human. Although toxicological profiles derived from non-clinical studies must be considered before any final decision is made, our work will facilitate clinical studies on SMA. | - |
dc.format.extent | 11 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | KOREAN SOC APPLIED PHARMACOLOGY | - |
dc.title | Calculation of a First-In-Man Dose of 7-O-Succinyl Macrolactin A Based on Allometric Scaling of Data from Mice, Rats, and Dogs | - |
dc.type | Article | - |
dc.identifier.doi | 10.4062/biomolther.2016.192 | - |
dc.identifier.bibliographicCitation | BIOMOLECULES & THERAPEUTICS, v.25, no.06, pp 648 - 658 | - |
dc.identifier.kciid | ART002280005 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000415274600012 | - |
dc.identifier.scopusid | 2-s2.0-85033557732 | - |
dc.citation.endPage | 658 | - |
dc.citation.number | 06 | - |
dc.citation.startPage | 648 | - |
dc.citation.title | BIOMOLECULES & THERAPEUTICS | - |
dc.citation.volume | 25 | - |
dc.type.docType | Article | - |
dc.publisher.location | 대한민국 | - |
dc.subject.keywordAuthor | 7-O-Succinyl macrolactin A | - |
dc.subject.keywordAuthor | Pharmacokinetics | - |
dc.subject.keywordAuthor | First-In-Man dose | - |
dc.subject.keywordAuthor | Allometric scaling | - |
dc.subject.keywordAuthor | Dienetichron plot | - |
dc.subject.keywordPlus | BACILLUS-POLYFERMENTICUS KJS-2 | - |
dc.subject.keywordPlus | PHARMACOKINETIC PARAMETERS | - |
dc.subject.keywordPlus | LIQUID-CHROMATOGRAPHY | - |
dc.subject.keywordPlus | DRUG DEVELOPMENT | - |
dc.subject.keywordPlus | HUMANS | - |
dc.subject.keywordPlus | PLASMA | - |
dc.subject.keywordPlus | METABOLISM | - |
dc.subject.keywordPlus | PREDICTION | - |
dc.subject.keywordPlus | CLEARANCE | - |
dc.subject.keywordPlus | CAFFEINE | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
84, Heukseok-ro, Dongjak-gu, Seoul, Republic of Korea (06974)02-820-6194
COPYRIGHT 2019 Chung-Ang University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.