Role of Pharmacokinetic Studies in Drug Discovery

Toomula, Nishant; D, Sathish Kumar; Kumar, Arun; Phaneendra, M

doi:10.4172/jbb.1000097

Cited by 14 publications

(8 citation statements)

References 53 publications

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“…Absorption features outlined that HSP is moderately soluble in water (QPlogPo/w ¼ 1.803), moderate Caco-2 permeable, 75.45% absorbed human orally, act as a P-glycoprotein substrate, and have good skin penetrability (QPlogKp ¼ -4.071). Distribution refers to drug movement within the body and depends on several factors i,e, BBB permeability, CNS permeability, binding to plasma protein, and many more [141]. Our predicted result suggested that HSP has the potentiality to cross the blood-brain barrier (QPlogBB ¼ -1.512), penetrate to CNS (CNS ¼ -2), and have a high affinity to bind with Human serum albumin (QPlogKhsa ¼ 0.018).…”

Section: Pharmacokinetics and Future Perspective In Drug Developmentmentioning

confidence: 93%

“…Pharmacokinetic studies help determine the effects of respective drugs in the body based on absorption, distribution, metabolism, excretion, and toxicity. These pharmacokinetic properties are called ADMET [141]. Analysis of these properties aid in designing a drug to treat numerous diseases in medical society with understanding potential risk, time, and cost to determine whether or not a compound is suitable to proceed to the clinical stage.…”

Section: Pharmacokinetics and Future Perspective In Drug Developmentmentioning

confidence: 99%

“…It was observed that HSP was found to meet all tested i,e Lipinski, Jorgensen's, Ghose, Egan, Veber, and Muegge rules with a good bioavailability score (0.55), indicated maintained Drug likeness properties. The absorption of drugs is an essential property for entering blood circulation and practical activities [141]. Absorption features outlined that HSP is moderately soluble in water (QPlogPo/w ¼ 1.803), moderate Caco-2 permeable, 75.45% absorbed human orally, act as a P-glycoprotein substrate, and have good skin penetrability (QPlogKp ¼ -4.071).…”

Section: Pharmacokinetics and Future Perspective In Drug Developmentmentioning

confidence: 99%

See 2 more Smart Citations

Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: A comprehensive review

Sohel

Sultana

et al. 2022

Heliyon

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Hesperetin is potential natural compound for its attributes in various anticancer activities. Hesperetin can modulate diverse signaling pathways in cancer cells related to growth, metastasis, and apoptosis. Hesperetin also increases chemosensitivity in chemotherapy in a synergistic approach. Hesperetin processes less toxicity in human body but more bioavailability, conferring its application in clinical settings.

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Section: Pharmacokinetics and Future Perspective In Drug Developmentmentioning

confidence: 93%

Section: Pharmacokinetics and Future Perspective In Drug Developmentmentioning

confidence: 99%

Section: Pharmacokinetics and Future Perspective In Drug Developmentmentioning

confidence: 99%

See 1 more Smart Citation

Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: A comprehensive review

Sohel

Sultana

et al. 2022

Heliyon

View full text Add to dashboard Cite

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“…After absorption, consequentially comes distribution, another principal descriptor for drug development, which depends mumerous factors i.e., steady-state volume of distribution (VDss), blood-brain barrier (BBB) and central nervous system(CNS) permeability, binding to plasma protein, and many more [117].Our analysis suggested that Gen has the potentiality to have a poor…”

Section: Clinical Trialsmentioning

confidence: 94%

Genistein Mediated Molecular Pharmacology, Cell-Specific Anti-Breast Cancer Mechanism with Synergistic Effect and in silico Safety Measurement

Sohel¹,

Biswas²,

Amin³

et al. 2021

Preprint

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Breast cancer (BC) is the most common type of cancer in both men and women alike, but it is more prevalent in women. Natural compounds that can modulate the oncogenic process can be considered a significant anti-cancer agent for treating BC. These natural compounds are more effective than synthetic drugs, which have profound side effects on the normal cell and resistance to cancer cells. Genistein is a type of dietary phytoestrogen included in the flavonoid group with a similar structure of estrogen that might provide a strong alternative and complementary medicine to existing chemotherapeutics drugs. Several research studies demonstrated that it can target the estrogen receptor (ER), Human epidermal growth factor receptor-2 (HER2), and Breast cancer gene-1 (BRCA-1) in multiple BC cell lines, as well as sensitize cancer cell lines to this compound when used at an optimal inhibitory concentration. Genistein effectively showed anti-cancer activities through apoptosis induction, arresting cell cycle, inhibiting angiogenesis with metastasis, reducing inflammation, mammosphere formation, tumor growth, up-regulating tumor suppressor gene, and downregulating oncogene in suppressing cancer progression in vitro and animal model study. In addition, research studies have also suggested that these phytochemicals synergistically reverse the resistance mechanism of chemotherapeutic drugs, increasing the efficacy of some chemoinformatics drugs. Our review article aims to unbox and validate the molecular pharmacology in breast tissue, cell-specific anti-cancer mechanism with synergistic activity, and possible pharmacokinetic parameters of Genistein as a potential alternative therapeutic option for the treatment of BC.

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“…Due to the emergence and spread of multidrug-resistant bacteria, the development of new drugs for use in animals and humans has become increasingly necessary. In this context, pharmacokinetic studies are an important and indispensable step of drug development [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Plasma Protein Binding Rate and Pharmacokinetics of Lekethromycin in Rats

et al. 2022

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Lekethromycin (LKMS), a novel macrolide lactone, is still unclear regarding its absorption. Thus, we conducted this study to investigate the characteristics of LKMS in rats. We chose the ultrafiltration method to measure the plasma protein binding rate of LKMS. As a result, LKMS was characterized by quick absorption, delayed elimination, and extensive distribution in rats following intramuscular (im) and subcutaneous (sc) administration. Moreover, LKMS has a high protein binding rate (78–91%) in rats at a concentration range of 10–800 ng/mL. LKMS bioavailability was found to be approximately 84–139% and 52–77% after im and sc administration, respectively; however, LKMS was found to have extremely poor bioavailability after oral administration (po) in rats. The pharmacokinetic parameters cannot be considered linearly correlated with the administered dose. Additionally, LKMS and its corresponding metabolites were shown to be metabolically stable in the liver microsomes of rats, dogs, pigs, and humans. Notably, only one phase I metabolite was identified during in vitro study, suggesting most of drug was not converted. Collectively, LKMS had quick absorption but poor absorption after oral administration, extensive tissue distribution, metabolic stability, and slow elimination in rats.

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Role of Pharmacokinetic Studies in Drug Discovery

Cited by 14 publications

References 53 publications

Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: A comprehensive review

Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: A comprehensive review

Genistein Mediated Molecular Pharmacology, Cell-Specific Anti-Breast Cancer Mechanism with Synergistic Effect and in silico Safety Measurement

Plasma Protein Binding Rate and Pharmacokinetics of Lekethromycin in Rats

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