title: Salvianolic acid B as a substrate and weak catechol-O-methyltransferase inhibitor in rats.
abstract: 1. The aim of this study was to investigate the biotransformation of salvianolic acid B (SAB) by catechol-O-methyltransferase (COMT) and its interaction with levodopa (l-DOPA) methylation in rats. 2. The enzyme kinetics of SAB were studied after incubation with rat COMT. The in vivo SAB and 3-monomethyl-SAB (3-MMS) levels were determined after a single dose of tolcapone with or without SAB administration. For l-DOPA, the effect of SAB inhibition on l-DOPA methylation was studied in vitro. The l-DOPA and 3-O-methyldopa (3-OMD) levels were determined after single and multiple doses of SAB with or without l-DOPA administration. 3. After incubation, we found that SAB was methylated mainly by rat liver and kidney COMT. Tolcapone strongly inhibited the formation of 3-MMS in vitro and in vivo, without any change in the plasma concentration of SAB. Moreover, tolcapone significantly increased the cumulative bile excretion of SAB from 3% to 40% in the rat. SAB inhibited the methylation of l-DOPA with an IC50 value of 2.08 μM in vitro. In vivo, a single intravenous dose of SAB decreased the plasma concentration of 3-OMD, with no obvious effect on the pharmacokinetics of l-DOPA. Multiple doses of SAB given to rats also decreased the plasma concentration of 3-OMD, while SAB increased the plasma concentration of l-DOPA.
authors: a State Key Laboratory of Natural Medicines, Jiangsu Province Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University , Nanjing , China.
authors: Qu
authors: Q
authors: Qi
authors: Lijuan
authors: L
authors: Cao
authors: Feiyan
authors: F
authors: Li
authors: Hong
authors: H
authors: Wang
authors: Huiying
authors: H
authors: Liu
authors: Haiping
authors: H
authors: Hao
authors: Kun
authors: K
authors: Hao
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001577:Benzophenones / Q000494:pharmacology; D002394:Catechol O-Methyltransferase; D065098:Catechol O-Methyltransferase Inhibitors / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000378:metabolism; D007700:Kinetics; D007980:Levodopa / Q000378:metabolism; D008297:Male; D055442:Metabolome / Q000187:drug effects; D008745:Methylation / Q000187:drug effects; D009596:Nitrophenols / Q000494:pharmacology; D009928:Organ Specificity / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013379:Substrate Specificity / Q000187:drug effects; D000077867:Tolcapone; D014443:Tyrosine / Q000031:analogs & derivatives; D053630:Depsides
chemical_list: D001572:Benzofurans; D001577:Benzophenones; D002394:Catechol O-Methyltransferase; D065098:Catechol O-Methyltransferase Inhibitors; D004295:Dihydroxyphenylalanine; D007980:Levodopa; D009596:Nitrophenols; D000077867:Tolcapone; D014443:Tyrosine; C076944:salvianolic acid B; D053630:Depsides; C008404:3-methoxytyrosine
keywords: Catechol-O-methyltransferase; levodopa; methylation; pharmacokinetics; salvianolic acid B