Naproxen glycine conjugate-synthesis, pharmaceutical preformulation and pharmacodynamic evaluation

Mishra, Abha; Agrawal, Shalini; Pathak, Kamla

doi:10.3109/10717544.2011.649218

Cited by 14 publications

(7 citation statements)

References 18 publications

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“…63 While the release of parent or metabolites in the free form may be a source of exposure, 64,73 the amino acid conjugates themselves may also confer toxicological effects. 69,74 For example, a variety of amino acid conjugates of naproxen and ibuprofen were found to have similar biological activity to the parent in vivo in rats. 74 The glycine and glutamine conjugates of several other carboxylic acids also showed acute toxicity to mice or rat that was comparable to that of the parent on a molar basis.…”

Section: ■ Discussionmentioning

confidence: 99%

“…In addition, human gut microbiota, enterocytes and hepatocytes are known to express enzymes such as aminoacylases, dipeptidases, and glucuronidases that may cleave conjugates. ,− For instance, amino acid conjugates of salicylic acid were stable in the upper gastrointestinal tract but were hydrolyzed in the colon to release the active parent salicylic acid . Glycine conjugate of naproxen was found to exhibit 78.5% reversion to naproxen by fecal content in vitro . In general, the deconjugation rate of amino acid conjugates varied from 52.6% to 96.5%. ,,− Indeed, the daily intake of naproxen, if estimated by considering the conjugation fraction in Arabidopsis seedlings and deconjugation rates, would be 752 ng/kg of body weight/day using the same input values as in Prosser and Sibley .…”

Section: Discussionmentioning

confidence: 99%

“…Glycine conjugate of naproxen was found to exhibit 78.5% reversion to naproxen by fecal content in vitro . In general, the deconjugation rate of amino acid conjugates varied from 52.6% to 96.5%. ,,− Indeed, the daily intake of naproxen, if estimated by considering the conjugation fraction in Arabidopsis seedlings and deconjugation rates, would be 752 ng/kg of body weight/day using the same input values as in Prosser and Sibley . The calculated adult hazard quotient would become 0.11, which is 11 times larger than that derived solely from the parent compound (Text S4).…”

Section: Discussionmentioning

confidence: 99%

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Direct Conjugation of Emerging Contaminants in Arabidopsis: Indication for an Overlooked Risk in Plants?

Zhang

Borchardt³

et al. 2017

Environ. Sci. Technol.

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Agricultural use of treated wastewater, biosolids, and animal wastes introduces a multitude of contaminants of emerging concerns (CECs) into the soil-plant system. The potential for food crops to accumulate CECs depends largely on their metabolism in plants, which at present is poorly understood. Here, we evaluated the metabolism of naproxen and ibuprofen, two of the most-used human drugs from the Profen family, in Arabidopsis thaliana cells and the Arabidopsis plant. The complementary use of high-resolution mass spectrometry and C labeling allowed the characterization of both free and conjugated metabolites, as well as nonextractable residues. Naproxen and ibuprofen, in their parent form, were conjugated quickly and directly with glutamic acid and glutamine, and further with peptides, in A. thaliana cells. For example, after 120 h, the metabolites of naproxen accounted for>90% of the extractable chemical mass, while the intact parent itself was negligible. The structures of glutamate and glutamine conjugates were confirmed using synthesized standards and further verified in whole plants. Amino acid conjugates may easily deconjugate, releasing the parent molecule. This finding highlights the possibility that the bioactivity of such CECs may be effectively preserved through direct conjugation, a previously overlooked risk. Many other CECs are also carboxylic acids, such as the profens. Therefore, direct conjugation may be a common route for plant metabolism of these CECs, making it imperative to consider conjugates when assessing their risks.

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Section: ■ Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Direct Conjugation of Emerging Contaminants in Arabidopsis: Indication for an Overlooked Risk in Plants?

Zhang

Borchardt³

et al. 2017

Environ. Sci. Technol.

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“…Despite limitations associated with oral administration, naproxen has a high bioavailability of 95% when orally ingested 288 with most of the drug reaching the systemic circulation system in active form. 289 However there are concerns of severe toxic effects from overuse or over dose such as nausea, abdominal pain, and peptic ulcers. 290,291 Naproxen toxicity and adverse effects can be limited by appropriated encapsulation and as such various research groups have investigation the potential to reduce toxicity.…”

Section: Naproxenmentioning

confidence: 99%

Towards Smart Drug Delivery: Exploration of a Molecularly Imprinted Polymer Network

Khan¹

2023

Preprint

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The current study explores the concept of Molecular Imprinting Technology (MIT) and evaluates the ability of a molecularly imprinted hydrogel polymer (MIP) to preferentially uptake the template drug propranolol from aqueous solution. The extent of the molecular affinity and recognition was challenged by introducing a secondary competing structure during uptake. The release of propranolol as a response to environmental stimuli was investigated. The MIP was synthesized with copolymers methyl methacrylate (MMA) and N,N-dimethyl acrylamide (DMAA). Morphology was studied by scanning electron microscopy (SEM), ptake, displacement, and release experiments were studied by fluorescence spectroscopy. The SEM studies did not indicate the presence of molecularly imprinted cavities. The MIPs demonstrated preferential uptake in comparison to the non-imprinted (NIP) counterpart. The displacement studies revealed that uptake by the MIP is not very selective. The release studies demonstrated that ropranolol release can be tailored to respond to environmental stimuli such as temperature and, especially, pH.

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“…Additionally, the bioavailability of atorvastatin was increased by fivefold with conjugate as compared to its suspension form (Anwar et al 2011). In another study, amino acid conjugate of naproxen was synthesized to evaluate the effect on solubility and dissolution capability (Mishra et al 2012). The naproxen-glycine conjugates enhanced solubility and intrinsic dissolution of naproxen by 1.24-fold and 30.9%, respectively as compared to naproxen only with enhanced therapeutic effects (Mishra et al 2012).…”

Section: Derivatizationmentioning

confidence: 99%

Analysis and optimization of drug solubility to improve pharmacokinetics

Thapa

Choi

Kim

et al. 2017

Journal of Pharmaceutical Investigation

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Naproxen glycine conjugate-synthesis, pharmaceutical preformulation and pharmacodynamic evaluation

Cited by 14 publications

References 18 publications

Direct Conjugation of Emerging Contaminants in Arabidopsis: Indication for an Overlooked Risk in Plants?

Direct Conjugation of Emerging Contaminants in Arabidopsis: Indication for an Overlooked Risk in Plants?

Towards Smart Drug Delivery: Exploration of a Molecularly Imprinted Polymer Network

Analysis and optimization of drug solubility to improve pharmacokinetics

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