Pharmacokinetic, bioavailability, metabolism and plasma protein binding evaluation of NADPH-oxidase inhibitor apocynin using LC–MS/MS

Chandasana, Hardik; Chhonker, Yashpal S.; Bala, Veenu; Prasad, Yarra Durga; Telaprolu, Krishna; Sharma, Vishnu L.; Bhatta, Rabi Sankar

doi:10.1016/j.jchromb.2015.01.025

Cited by 28 publications

(20 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Equilibrium dialysis (ED) is typically regarded as the ‘gold standard’ approach to determine PPB . PPB study was performed as per previously reported ED method with slight modifications . Before proceeding with PPB study, stability of E ‐ and Z ‐guggulsterone was assesd in plasma.…”

Section: Methodsmentioning

confidence: 99%

“…[34] PPB study was performed as per previously reported ED method with slight modifications. [35,36] Before proceeding with PPB study, stability of E-and Z-guggulsterone was assesd in plasma. Non-specific binding potential of E-and Z-gugglsterone to dialysis membrane and cells was assessed by spiking them into tris buffer and incubating for 10 h. E-and Z-guggulsterone were stable in plasma for 10 h and showed no non-specific binding to dialysis membrane or cell.…”

Section: Plasma Protein Binding (Ppb) Study Using Equilibrium Dialysimentioning

confidence: 99%

See 1 more Smart Citation

Assessment of in vitro metabolic stability, plasma protein binding, and pharmacokinetics of E‐ and Z‐guggulsterone in rat

Chhonker

Chandasana

Mukkavilli

et al. 2015

Drug Testing and Analysis

Self Cite

View full text Add to dashboard Cite

Guggulsterone is a racemic mixture of two stereoisomers (E- and Z-), obtained from the gum resin of Commiphora mukul and it is marketed as an antihyperlipidemic drug. The aim of our study was to assess the in vitro and in vivo absorption, distribution, metabolism, and excretion (ADME) properties namely solubility, in vitro metabolism, plasma protein binding and oral pharmacokinetic studies of E- and Z-guggulsterone. In vitro metabolism experiments were performed by using rat liver and intestinal microsomes. In vitro intrinsic clearance (CLint ) was found to be 33.34 ± 0.51 and 39.23 ± 8.12 μL/min/mg protein in rat liver microsomes for E- and Z-isomers, respectively. Plasma protein binding was determined by equilibrium dialysis method and in vivo pharmacokinetic studies were performed in male Sprague Dawley (SD) rats. Both isomers were highly bound to rat plasma proteins (>95% bound). Plasma concentration of E- and Z-isomers decreased rapidly following oral administration and were eliminated from systemic circulation with a terminal half-life of 0.63 ± 0.25 and 0.74 ± 0.35 h, respectively. The clearance (CL) for E-isomer was 2.79 ± 0.73 compared to 3.01 ± 0.61 L/h/kg for Z-isomer, indicating no significant difference (student t test; p <0.05) in their elimination.The pharmacokinetics of both isomers was characterized by extensive hepatic metabolism as seen with rat liver microsomes with high clearance and low systemic availability in rats. In brief, first-pass metabolism seems to be responsible factor for low bioavailability of guggulsterone. Copyright © 2015 John Wiley & Sons, Ltd.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Plasma Protein Binding (Ppb) Study Using Equilibrium Dialysimentioning

confidence: 99%

Assessment of in vitro metabolic stability, plasma protein binding, and pharmacokinetics of E‐ and Z‐guggulsterone in rat

Chhonker

Chandasana

Mukkavilli

et al. 2015

Drug Testing and Analysis

Self Cite

View full text Add to dashboard Cite

show abstract

“…PPB is the distribution indicative of unbound drug which reflects the pharmacodynamically active drug with consequences in overall pharmacological action. The knowledge of plasma protein binding remains important throughout a drug discovery and development project, but should be integrated to pharmacokinetic data [9,18,29]. There are several in vitro methods for measuring the unbound fraction in plasma and, ultrafiltration is one of the most commonly used [27].…”

Section: Conditionsmentioning

confidence: 99%

“…Pharmacokinetics and metabolism studies play a notable role in early drug discovery and development process [9]. Over the last decade, these studies have been responsible, for the decrease in the failure rate of drug development [10].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic properties, in vitro metabolism and plasma protein binding of govaniadine an alkaloid isolated from Corydalis govaniana Wall

Marques

Callejon

Pinto³

et al. 2016

Journal of Pharmaceutical and Biomedical Analysis

View full text Add to dashboard Cite

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, with a lower limit of quantitation (LLOQ) of 2.5ngmL. 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, 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.

show abstract

“…Pharmacokinetic, bioavailability and metabolism of acetovallione in human has been evaluated recently (Chandasana et al, 2015). Acetovallione may be administered orally in a controlled manner along with hydration therapy as it is reported successfully in rat (Wang et al, 2008).…”

Section: Acetovanillone and Cisplatin Synergistically Effect Cell Deamentioning

confidence: 99%

Pharmacological inhibition of NADPH oxidase protects against cisplatin induced nephrotoxicity in mice by two step mechanism

Wang

Luo²,

Pān

et al. 2015

Food and Chemical Toxicology

View full text Add to dashboard Cite

Pharmacokinetic, bioavailability, metabolism and plasma protein binding evaluation of NADPH-oxidase inhibitor apocynin using LC–MS/MS

Cited by 28 publications

References 17 publications

Assessment of in vitro metabolic stability, plasma protein binding, and pharmacokinetics of E‐ and Z‐guggulsterone in rat

Assessment of in vitro metabolic stability, plasma protein binding, and pharmacokinetics of E‐ and Z‐guggulsterone in rat

Pharmacokinetic properties, in vitro metabolism and plasma protein binding of govaniadine an alkaloid isolated from Corydalis govaniana Wall

Pharmacological inhibition of NADPH oxidase protects against cisplatin induced nephrotoxicity in mice by two step mechanism

Contact Info

Product

Resources

About