In-situ absorption, protein binding and pharmacokinetic studies of S002-853, a novel antidiabetic and antidyslipidaemic flavone derivative in rats

Gautam, Nagsen; Kushwaha, Hari Narayan; Pratap, Ramendra; Singh, Shio Kumar

doi:10.1211/jpp.62.05.0007

Cited by 4 publications

(2 citation statements)

References 14 publications

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“…In addition, multiple peaks were observed in plasma concentration–time profiles after a single administration. This may be due to enterohepatic recycling, selective and differential absorption from the gastrointestinal tract, and the formation of a depot on the intestinal wall and/or variation in gastrointestinal motility (Gautam, Kushwaha, Pratap, & Singh, ). PK parameters for single and multiple dose administration studies were found to be statistically comparable (Table ), indicating no plasma accumulation of 99/411 after multiple dose administration.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic studies of a novel trioxane antimalarial (99/411) in rats and monkeys using LC–MS/MS

Pandey

Gautam

Kushwaha

et al. 2016

Biomedical Chromatography

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The pharmacokinetic profile of 99/411, a novel anti-malarial drug, was established in rats (12 mg/kg of body weight) and monkeys (20 mg/kg of body weight). Following oral administration, the presence of 99/411 was rapidly determined in rat plasma, tissues, urine, feces and monkey plasma using a validated LC-MS/MS method. The tissue distribution studies in rats indicated that the drug was partially distributed in all major tissues and plasma, and peak concentration levels were achieved within 0.5-4 h. Area under the curve in different rat tissues and plasma was found in order of blood > lung > intestine > heart > muscle > brain > kidney > spleen > liver. The total recoveries (within 86 h) of 99/411 were <0.0017% and <0.08% in urine and feces, respectively. The peak plasma concentration was 3499 ng/mL in rats after ~2 h of oral administration and 697-767 ng/mL in monkeys after ~6 h of oral administration. No plasma accumulation was observed in both male and female monkeys, even after multiple dosing. The preclinical pharmacokinetic profile and tissue distribution data are expected to assist in future clinical explorations of 99/411 as a promising anti-malarial agent.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic studies of a novel trioxane antimalarial (99/411) in rats and monkeys using LC–MS/MS

Pandey

Gautam

Kushwaha

et al. 2016

Biomedical Chromatography

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“…The elimination halflife (t 1/2 ) and mean residence time (MRT) were 3.39 h and 5.96 h, respectively. The previous published data for antidiabetic flavone derivatives show a higher systemic exposure and higher elimination half-life compared to S002-857 [17]. The pharmacokinetics of flavonoids have been an area of active research in the last decade.…”

Section: Applicationmentioning

confidence: 97%

LC-MS/MS Assay for Quantification of a Novel Antidiabetic Flavone Derivative S002-857 in Rat Plasma, Urine and Feces: Application in Pharmacokinetic Studies

et al. 2011

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This study aimed to develop an LC-MS/MS assay for the quantitation of S002-857 in plasma, urine and feces to evaluate the pharmacokinetic parameters and elimination pathway for further development of S002-857. A sensitive and selective LC-MS/MS method was developed and validated for estimating a novel antidiabetic flavone derivative, S002-857, synthesized by Central Drug Research Institute, CSIR, Lucknow, India. Plasma and urine samples were prepared by two-step liquid-liquid extraction with diethyl ether and feces by protein precipitation using acetonitrile. The analyte was chromatographed on a cyano column with methanol-ammonium acetate buffer (pH 4.6, 10 mM; 90:10, v/v). The calibration curves were linear over a range of 0.78-400 ng mL -1 for plasma and 1.56-400 ng mL -1 for urine and feces samples. The accuracy and precision were \15% for plasma, urine and feces samples. The recoveries from spiked plasma, urine and feces samples were [85%. S002-857 was stable in plasma for 8 h at ambient temperature, 30 days at -60°C and after three freeze-thaw cycles. The assay was successfully applied to determine the pharmacokinetic parameters and excretion profile in male rats.

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Development and validation of UPLC-MS/MS assay for quantification of cladrin: Absolute bioavailability and dose proportionality study in rats

Rashid

Singh

Malik

et al. 2018

Journal of Pharmaceutical and Biomedical Analysis

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In-situ absorption, protein binding and pharmacokinetic studies of S002-853, a novel antidiabetic and antidyslipidaemic flavone derivative in rats

Abstract: In-situ study of S002-853 shows slow absorption from the gastrointestinal tract. S002-853 also shows low plasma protein binding. The pharmacokinetic parameters after oral and intravenous dose reveal low oral bioavailability and high mean residence time.

Cited by 4 publications

References 14 publications

Pharmacokinetic studies of a novel trioxane antimalarial (99/411) in rats and monkeys using LC–MS/MS

Pharmacokinetic studies of a novel trioxane antimalarial (99/411) in rats and monkeys using LC–MS/MS

LC-MS/MS Assay for Quantification of a Novel Antidiabetic Flavone Derivative S002-857 in Rat Plasma, Urine and Feces: Application in Pharmacokinetic Studies

Development and validation of UPLC-MS/MS assay for quantification of cladrin: Absolute bioavailability and dose proportionality study in rats

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