Evaluation of oral pharmacokinetics, in vitro metabolism, blood partitioning and plasma protein binding of novel antidiabetic agent, S009‐0629 in rats

Valicherla, Guru R.; Italiya, Kishan S.; Gupta, C. P.; Mishra, Shachi; Riyazuddin, Mohammed; Syed, Anees A.; Singh, Sandeep K.; Shahi, Sudhir; Taneja, Gaurav; Wahajuddin, Mohammad; Goel, Atul; Gayen, Jiaur R.

doi:10.1002/ddr.21433

Cited by 3 publications

(1 citation statement)

References 18 publications

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“…Both generated as well as reference plasma samples (100 μL) were processed with ACN and analyzed with UPLC. The hematocrit (Hc) for the whole blood and the red blood cells (RBCs): plasma partition coefficient (K RBC/PL ) for WA was calculated using Equations and , respectively (Mehrotra, Lal, Puri, Madhusudanan, & Gupta, ; Valicherla et al, )

Hc = \frac{Volume of blood cells}{Total blood volume}

KRBC / PL = \frac{1}{H} ([], \frac{normalI REF}{normalI PL} - 1)

…”

Section: Methodsmentioning

confidence: 99%

Determination of permeability, plasma protein binding, blood partitioning, pharmacokinetics and tissue distribution of Withanolide A in rats: A neuroprotective steroidal lactone

Singh

Valicherla

Joshi

et al. 2018

Drug Development Research

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Preclinical Research & Development Withanolide A (WA), a steroidal lactone is a major bioactive constituent of Withania somnifera (L.) with remarkable neuropharmacological activity. In this study, we investigated the permeability, plasma protein binding (PPB), blood partitioning, intravenous (i.v.), and oral pharmacokinetics as well as i.v. tissue distribution (TD) of pure WA in a rat model. The PPB, RBCs partitioning, and permeability of WA were determined by Ultra Performance Liquid Chromatography (UPLC) method. However, the pharmacokinetics and TD of WA were evaluated by validated and sensitive liquid chromatography coupled mass spectrometry (LC‐ESI‐MS/MS) method. The PPB and permeability of WA were determined by equilibrium dialysis and parallel artificial membrane permeability assay method, respectively. The results demonstrated that WA has high PPB and passive permeability. Furthermore, WA was found to have fast equilibration between RBCs and plasma. Following i.v. (2 mg/kg) and per‐oral (25 mg/kg) administration of WA, the max concentration (Cmax) in plasma was found as 85.53 ± 6.54 and 48.04 ±5.78 ng/mL, respectively. The TD study results indicated that WA has a rapid and wide TD. The maximum concentration in various tissues was found in following order: Clung > Cliver > Ckidney ≈ Cspleen > Cheart > Cbrain. The preclinical in vitro, as well as pharmacokinetics and TD results, are anticipated to support the future preclinical and clinical application of WA.

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Hc = \frac{Volume of blood cells}{Total blood volume}

KRBC / PL = \frac{1}{H} ([], \frac{normalI REF}{normalI PL} - 1)

…”

Section: Methodsmentioning

confidence: 99%

Determination of permeability, plasma protein binding, blood partitioning, pharmacokinetics and tissue distribution of Withanolide A in rats: A neuroprotective steroidal lactone

Singh

Valicherla

Joshi

et al. 2018

Drug Development Research

Self Cite

View full text Add to dashboard Cite

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Preclinical pharmacokinetic exploration of a novel osteoporotic quinazolinone-benzopyran-indole hybrid (S019-0385) using LC-MS/MS

Kumar,

Chauhan,

Verma

et al. 2023

Xenobiotica

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LC–MS/MS method for quantification of raspberry ketone in rat plasma: application to preclinical pharmacokinetic studies

et al. 2023

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Background: Raspberry ketone (RK), derived from red raspberry fruit ( Rubus idaeus, family Rosaceae), is a reported potent antiobesity agent. This study aims to investigate method development, validation, and in vitro and in vivo pharmacokinetics in rats. Materials & methods: LC–MS/MS was used to conduct method development, validation, stability, and oral PK samples of RK in plasma analyses. Results: RK was highly soluble in Tris buffer and stable in gastrointestinal fluids as well as plasma. Rat liver microsomal stability of RK in phase I and II studies was 84.96 ± 2.39 and 69.98 ± 8.69%, respectively, after 60 min. Intestinal permeability was 4.39 ± 1.37 × 10-5 cm/s. Maximal concentration was 1591.02 ± 64.76 ng/ml, which was achieved after 1 h (time to maximal concentration), and absolute oral bioavailability was 86.28%. Conclusion: Pharmacokinetic data serve as a keystone for preclinical and clinical adjuvant therapy.

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Evaluation of oral pharmacokinetics, in vitro metabolism, blood partitioning and plasma protein binding of novel antidiabetic agent, S009‐0629 in rats

Cited by 3 publications

References 18 publications

Determination of permeability, plasma protein binding, blood partitioning, pharmacokinetics and tissue distribution of Withanolide A in rats: A neuroprotective steroidal lactone

Determination of permeability, plasma protein binding, blood partitioning, pharmacokinetics and tissue distribution of Withanolide A in rats: A neuroprotective steroidal lactone

Preclinical pharmacokinetic exploration of a novel osteoporotic quinazolinone-benzopyran-indole hybrid (S019-0385) using LC-MS/MS

LC–MS/MS method for quantification of raspberry ketone in rat plasma: application to preclinical pharmacokinetic studies

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