<i>In vitro</i> metabolism and <i>in vivo</i> pharmacokinetics of bentysrepinine (Y101), an investigational new drug for anti-HBV-infected hepatitis: focus on interspecies comparison
Creators: name: Fan, Huirong
name: Zhang, Aijie
name: Liao, Cuiping
name: Yang, Yuanhui
name: Zhang, Lihua
name: Liu, Jianfeng
name: Xia, Yuanyuan
name: Si, Duanyun
name: Dong, Shiqi
name: Liu, Changxiao
Publisher: name: Taylor & Francis
Year: 2019
Subjects: subject: Biochemistry
subject: Physiology
subject: FOS: Biological sciences
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences

description: The objective of this study was to clarify the species differences of pharmacokinetics of Y101 (N-[N-benzoyl-O-(2-dimethylaminoethyl)-l-tyrosyl]-l-phenylalaninol hydrochloride), a derivative of herbal ingredient with anti-HBV hepatitis activity, in rats, dogs, monkeys and humans.The metabolic stability and metabolite identification studies using liver microsomes <i>in vitro</i>, plasma protein binding using a rapid equilibrium dialysis <i>in vitro</i>, pharmacokinetic studies <i>in vivo</i> were carried out to evaluate the interspecies differences. The toxicokinetic study in monkeys was also investigated.The metabolic profiles were similar in monkeys and humans, which were significant different from rats and dogs <i>in vitro</i>. <i>In vitro</i> plasma protein binding showed no major differences between species with medium to high protein binding rates. After single oral dose to rats, dogs, and monkeys, the absolute oral bioavailability of Y101 was 44.9%, 43.1%, and 19.2%, respectively. There was no accumulation for Y101 toxicokinetics in monkeys after oral administration for 90 d.The metabolic profiles indicated monkey was the very animal model for preclinical safety evaluation of Y101. Our results have demonstrated the favorable pharmacokinetics profile of Y101, which supports the clinical trials in humans. The objective of this study was to clarify the species differences of pharmacokinetics of Y101 (N-[N-benzoyl-O-(2-dimethylaminoethyl)-l-tyrosyl]-l-phenylalaninol hydrochloride), a derivative of herbal ingredient with anti-HBV hepatitis activity, in rats, dogs, monkeys and humans. The metabolic stability and metabolite identification studies using liver microsomes <i>in vitro</i>, plasma protein binding using a rapid equilibrium dialysis <i>in vitro</i>, pharmacokinetic studies <i>in vivo</i> were carried out to evaluate the interspecies differences. The toxicokinetic study in monkeys was also investigated. The metabolic profiles were similar in monkeys and humans, which were significant different from rats and dogs <i>in vitro</i>. <i>In vitro</i> plasma protein binding showed no major differences between species with medium to high protein binding rates. After single oral dose to rats, dogs, and monkeys, the absolute oral bioavailability of Y101 was 44.9%, 43.1%, and 19.2%, respectively. There was no accumulation for Y101 toxicokinetics in monkeys after oral administration for 90 d. The metabolic profiles indicated monkey was the very animal model for preclinical safety evaluation of Y101. Our results have demonstrated the favorable pharmacokinetics profile of Y101, which supports the clinical trials in humans.