Pharmacokinetic properties, in vitro metabolism and plasma protein binding of govaniadine an alkaloid isolated from Corydalis govaniana Wall.
Govaniadine (GOV) is an alkaloid isolated from Corydalis govaniana Wall. It has been reported to show a different number of biological activities including anti-urease, leishmanicidal and antinociceptive. The present study aims to characterize the GOV in vitro metabolism after incubation with rat and human liver microsomes (RLM and HLM, respectively) and to evaluate its pharmacokinetic properties. The identification of GOV metabolites was conducted by different mass analyzers: a micrOTOF II-ESI-ToF Bruker Daltonics®and an amaZon-SL ion trap (IT) Bruker Daltonics®. For the pharmacokinetic study of GOV in rats after intravenous administration, a LC-MS/MS method was developed and applied to. The analyses were performed using an Acquity UPLC®coupled to an Acquity TQD detector equipped with an ESI interface. The liver microsomal incubation resulted in new O-demethylated, di-hydroxylated and mono-hydroxylated compounds. Regarding the method validation, the calibration curve was linear over the concentration range of 2.5-3150.0ngmL-1, with a lower limit of quantitation (LLOQ) of 2.5ngmL-1. This method was successfully applied to a pharmacokinetic study. The profile was best fitted to a two-compartment model, the first phase with a high distribution rate constant (α) 0.139±0.086min-1, reflected by the short distribution half-life (t1/2α) 9.2±8.9min and the later one, with an elimination half-life (t1/2β) 55.1±37.9min. The main plasma protein binding was 96.1%. This is a first report in this field and it will be useful for further development of govaniadine as a drug candidate.
Departamento de Físico-Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903 Ribeirão Preto, São Paulo, Brazil.
Lucas M M
LMM
Marques
Departamento de Físico-Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903 Ribeirão Preto, São Paulo, Brazil.
Daniel R
DR
Callejon
Departamento de Físico-Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903 Ribeirão Preto, São Paulo, Brazil; Wolfson Centre for Age-Related Diseases, Kings College London, Guy's Campus, London Bridge, SE11UL-London, England.
Larissa G
LG
Pinto
Faculdade de Ciências Farmacêuticas de Araraquara, Departamento de Princípios Ativos Naturais e Toxicologia, Universidade Estadual Paulista Júlio de Mesquita Filho, 14801-902 Araraquara, São Paulo, Brazil.
Michel L
ML
de Campos
Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 14040-901 Ribeirão Preto, São Paulo, Brazil.
Anderson R M
ARM
de Oliveira
Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 14040-901 Ribeirão Preto, São Paulo, Brazil.
Ricardo
R
Vessecchi
HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Achyut
A
Adhikari
Amrit Science Campus, Tribhuvan University, Kathmandu, Nepal.
Ram L S
RLS
Shrestha
Faculdade de Ciências Farmacêuticas de Araraquara, Departamento de Princípios Ativos Naturais e Toxicologia, Universidade Estadual Paulista Júlio de Mesquita Filho, 14801-902 Araraquara, São Paulo, Brazil.
Rosangela G
RG
Peccinini
Departamento de Físico-Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903 Ribeirão Preto, São Paulo, Brazil. Electronic address: npelopes@gmail.com.
Norberto P
NP
Lopes
D000470:Alkaloids / Q000097:blood / Q000302:isolation & purification / Q000493:pharmacokinetics*; D000818:Animals; D031311:Corydalis; D006801:Humans; D059625:Liquid-Liquid Extraction / Q000379:methods; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010936:Plant Extracts / Q000097:blood / Q000302:isolation & purification / Q000493:pharmacokinetics*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013729:Terpenes / Q000097:blood / Q000302:isolation & purification / Q000493:pharmacokinetics*
D000470:Alkaloids; D010936:Plant Extracts; D013729:Terpenes; C000597094:govaniadine
Govaniadine; Pharmacokinetics; Two-compartment model; in vitro metabolism