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Vidyavathi, M.
- Biotransformation of Paracetamol by Cunninghamella echinulata
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Affiliations
1 Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women's University), Tirupati - 517 502, Andhra Pradesh, IN
1 Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women's University), Tirupati - 517 502, Andhra Pradesh, IN
Source
Journal of Pharmaceutical Research, Vol 8, No 1 (2009), Pagination: 1-5Abstract
The aim of the study was to develop a microbial model for synthesis of paracetamol metabolite for further pharmacological and toxicological studies. The metabolite of paracetamol in microbial cultures was identified, isolated and confirmed using fermentation techniques, Thin Layer Chromatography (TLC) and High Pressure Liquid Chromatography (HPLC) followed by liquid chromatography/mass spectrometry (LC/MS). Among different organisms screened, Cunninghamella echinulata showed an extra peak at 5.1 min in HPLC compared to its controls indicating formation of a metabolite. The metabolite was further characterized by mass spectrometry and was found to be N-acetyl-p-benzoquinoneimine (NAPQI) which is a toxic metabolite. Cunninghamella echinulata was able to metabolize paracetamol to its toxic metabolite by N-hydroxylation and rearrangement similar to human beings. This study has developed a model to produce toxic metabolites of other similar drugs easily for further toxicological and pharmacological studies.Keywords
Microbial Model, Metabolism, Paracetamol, N-Hydroxylation, NAPQI.Full Text
- Fungal Biotransformation of Clobazam–Induction, Inhibition and Kinetic Studies
Abstract Views :240 |
PDF Views:83
Authors
Affiliations
1 Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupathi 517 502, IN
1 Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupathi 517 502, IN
Source
Current Science, Vol 118, No 4 (2020), Pagination: 603-611Abstract
The present study was aimed to explore the ability of six distinct fungi to biotransform the drug clobazam to its metabolites, and the nature of enzymes involved in such fungal biotransformation by performing screening, induction, inhibition and kinetic studies. Among the six organisms, a sample of Aspergillus fumigatus culture showed an extra peak at 3.5 min in the high performance liquid chromatography chromatogram when compared with its controls, indicating the formation of metabolite. The metabolite thus formed was confirmed by mass spectrometry and NMR spectroscopy as 4-hydroxy norclobazam. Enzyme induction and inhibition studies were conducted on the involvement of a CYP3A4-like enzyme in fungal biotransformation. Enzyme kinetic studies were conducted to determine the affinity of the enzyme to the substrate. The study revealed that A. fumigatus can be used as a microbial resource to analyse the complete metabolic profile of clobazam with a maximum concentration 30 μg/ml.Keywords
Aspergillus Fumigatus, Biotransformation, Induction, Inhibition, Kinetics.Full Text
References
- Giarratano, M., Standley, K. and Benbadis S. R., Clobazam for treatment of epilepsy. Expert Opin. Pharmacother., 2012, 13, 227–233.
- DeLeon, J., Spina, E. and Diaz, F. J., Clobazam therapeutic drug monitoring: a comprehensive review of the literature with proposals to improve future studies. Ther. Drug Monit., 2013, 35, 30–47.
- Purcarin, G. and Ng, Y. T., Experience in the use of clobazam in the treatment of Lennox–Gastaut syndrome. Ther. Adv. Neurol. Disord., 2014, 7, 169–176.
- Giraud, C., Tran, A. and Rey, E., In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab. Dispos., 2004, 32(11), 1279–1286.
- Freche, C., Study of an anxiolytic, clobazam, in otorhinolaryngology in psychosomatic pharyngeal manifestations. Sem. Hop. Ther., 1975, 51(4), 261–263.
- Wildin, J. D., Pleuvry, B. J., Mawer, G. E., Onon, T. and Millington, L., Respiratory and sedative effects of clobazam and clonazepam in volunteers. Br. J. Clin. Pharmacol., 1990, 29(2), 169–177.
- Venisetty, R. K. and Ciddi, V., Application of microbial biotransformation for the new drug discovery using natural drugs as substrates. Curr. Pharm. Biotechnol., 2003, 4, 123–140.
- Chen, Y., Monshouwer, M. and Fitch, W. L., Analytical tools and approaches for metabolite identification in early drug discovery. Pharm. Res., 2007, 24, 248–257.
- Beukers, R., Marx, A. F. and Zuidweg, M. H. J., Microbial conversion as a tool in the preparation of drugs. In Drug Design (ed. Ariens, E. J.), Academic Press, New York, USA, 1972, vol. 3, p. 112.
- Smith, R. V. and Rosazza, J. P., Microbial models of mammalian metabolism. J. Pharm. Sci., 1975, 64, 1737–1758.
- Smith, R. V. and Rosazza, J. P., Microbial models of mammalian metabolism. J. Nat. Prod., 1983, 46, 79–91.
- Ratna Kumara, T., Vidyavathi, M., Asha, S. and Prasad, K. V. S. R. G., Biotransformation of paracetamol by Cunninghamella echinulata. J. Pharm. Res., 2009, 8(1), 1–5.
- Barry, M. and Feely, J., Enzyme induction and inhibition. Pharmacol. Ther., 1990, 48(1), 71–94.
- Wagner, J. G., Pharmacokinetics for the Pharmaceutical Scientist, Technomic Publishing Company, Lancaster, PA, USA, 1993, vol. 14, p. 259.
- Golicnik, M., Explicit reformulations of time-dependent solution for a Michaelis–Menten enzyme reaction model. Anal. Biochem., 2010, 406, 94–96.
- Dongming Wanga, B., Hongshan, Y., Jianguo Song, B., Yufeng X. and Fengxie Jin, B., Enzyme kinetics of ginsenosidase type IV hydrolyzing 6-O-multi-glycosides of protopanaxatriol type ginsenosides. Process Biochem., 2012, 47, 133–138.
- Lin, S. K. C., Du, C., Koutinas, A., Wang, R. and Webb, C., Substrate and product inhibition kinetics in succinic acid production by Actinobacillus succinogenes. Biochem. Eng. J., 2008, 41, 128–135.
- Maria Luz, C., Michaelis and Menten and the long road to the discovery of cooperativity. FEBS Lett., 2013, 587, 2767–2771.
- Deng, X., Marjorie, P., Marie, A. T., Wafa, K., Samuel, T., Jean Marie, F. and Jean Luc, P., Similarities and differences in the biochemical and enzymological properties of the four isomaltases from Saccharomyces cerevisiae. FEBS Open Bio., 2014, 4, 200–212.
- Maria Papadovasilaki, A., Dominik Oberthur, B., Renate Gessmann, A., Iosifina Sarrou, A., Christian Betzel, B., Effie Scoulica, C. N. and Kyriacos Petratos, A. N., Biophysical and enzymatic properties of amino glycoside adenylyltransferase AadA6 from Pseudomonas aeroginosa., BB Rep., 2015, 4, 152–157.
- Azerad, R., Microbial models for drug metabolism. Adv. Biochem. Eng. Biotechnol., 1999, 63, 169–218.
- Moody, J. D., Freeman, J. P., Fu, P. P. and Cerniglia, C. E., Biotransformation of mirtazapine by Cunninghamella elegans. Drug Metab. Dispos., 2002, 30, 1274–1279.
- Moffat, A. C., In Clarke’s Identification and Isolation of Drugs (eds Jackson, J. V. et al.), Pharmaceutical Press, London, UK, 1986, 2nd edn, p. 170.
- Walzer, M., Bekersky, I., Blum, R. A. and Tolbert, D., Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Pharmacotherapy, 2012, 32(4), 340–353.
- Yuh, L. et al., Substrate inhibition kinetics for cytochrome P450catalyzed reactions part 1. Drug Metab. Dispos., 2017, 29(4), 368–374.
- Brachet-Liermain, A., Jary, Ch., Faure, O., Guyot, M. and Loiseau, P., Liquid chromatography determination of clobazam and its major metabolite norclobazam in human plasma. Ther. Drug Monit., 1982, 4(3), 301–305.
- Sailaja, O., Aruna, R. and Durga, J., RP-HPLC Method development and validation for the estimation of clobazam in the tablet dosage form. Afro-Asian J. Sci. Technol., 2014, 1(2), 153–160.
- Effat, S., Amin Dastjani, F., Reza, A. and Mohsen, A., A stability indicating HPLC method for the determination of clobazam and its basic degradation product characterization. DARU J. Pharm. Sci., 2014, 22, 49–51.
- Segel, I. H., In Enzyme Kinetics: Behaviour and Analysis of Rapid Equilibrium and Steady State Enzyme Systems, Wiley, New York, USA, 1975, vol. 8, pp. 159–162.
- Magang, S. et al., Enzyme kinetics of cytochrome P450-mediated reactions. Curr. Drug Metab., 2000, 2, 17–36.
- Volz, M. et al., Kinetics and metabolism of clobazam in animals and man. Br. J. Clin. Pharmacol., 1979, 7, 41–50.
- Berg, J. M, Tymoczko J. L. and Stryer, L., In Biochemistry, New York W. H. Freeman, New York, USA, Section 8.4, The Michaelis–Menten model accounts for the kinetic properties of many enzymes, 5th edn, 2002; https://www.ncbi.nlm.nih.gov/books/NBK22430/.