Investigation of pharmacokinetic properties of a PEGylated bilirubin nanoparticle in male Sprague-Dawley rats using liquid chromatography-quadrupole time-of-flight mass spectrometry

Polyethylene glycol (PEG) was introduced into synthetic bilirubin 3α and a PEGylated bilirubin 3α nanoparticle (BX-001N, Brixelle®) was developed for the first time.An microsomal stability study, in vivo PK studies with intravenous bolus (IV) and subcutaneous injection (SC), and a semi-mass balance...

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Published inXenobiotica Vol. 54; no. 8; p. 563
Main Authors Park, Seo-Jin, Lim, Jeong-Hyeon, Lee, Jiyu, Lee, Jeongmin, Hwang, Sangsoo, Kim, Hyunjin, Jo, Seunghyun, Shin, Duckhyang, Ma, Sang Ho, Kim, Myung L, Shin, Young G
Format Journal Article
LanguageEnglish
Published England 13.09.2024
Subjects
Animals
Bilirubin - pharmacokinetics
Chromatography, Liquid
Male
Mass Spectrometry - methods
Microsomes, Liver - metabolism
Nanoparticles - chemistry
Polyethylene Glycols - chemistry
Polyethylene Glycols - pharmacokinetics
Rats
Rats, Sprague-Dawley
pharmacokinetic study
semi-mass balance study
BX-001N
Brixelle® bioanalysis
Pegylated synthetic bilirubin 3α nanoparticle
in vitro microsomal stability study
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Summary:Polyethylene glycol (PEG) was introduced into synthetic bilirubin 3α and a PEGylated bilirubin 3α nanoparticle (BX-001N, Brixelle®) was developed for the first time.An microsomal stability study, in vivo PK studies with intravenous bolus (IV) and subcutaneous injection (SC), and a semi-mass balance study of BX-001N were investigated to evaluate its pharmacokinetic (PK) properties in male Sprague-Dawley (SD) rats using developed liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-qTOF/MS).Following IV administration at 10 or 30 mg/kg, BX-001N showed very low clearance (0.33-0.67 mL/min/kg) with predominant distribution in the vascular system (Vd = 51.73-83.02 mL/kg). BX-001N was also very stable in vitro liver microsomal stability study.Following SC administration at 10 or 30 mg/kg, the bioavailability of BX-001N in plasma at 10 mg/kg was around 43% and showed the less dose-proportionality at 30 mg/kg dose.BX-001N was mainly excreted via the urinary pathway (86.59-92.99% of total amount of parent drug in excreta; urine and faeces) not via the biliary one.
ISSN:1366-5928
DOI:10.1080/00498254.2023.2284859