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İlaç Metabolizması ve Farmasötik Kimyada Önemi

Year 2016, Volume: 5 Issue: 2, 35 - 46, 01.10.2016

Abstract

İlaçların, organizmadaki enzimlerin etkisiyle kimyasal değişikliğe uğrayarak genellikle daha polar yeni bileşiklere dönüşmesine biyotransformasyon ya da metabolizma denir. Metabolizma sonucu, vücuda alınan ilaç ve diğer yabancı maddeler daha az toksik bir şekle dönüştürülür ve polar hale getirilerek en kısa sürede vücuttan atılır. Ayrıca bazı ilaçların etkileri, metabolizma sonucu oluşan metabolitlerinin farmakolojik etkileri nedeniyle görülmektedir. Bir ilacın piyasaya girebilmesi için metabolitlerinin izole edilmesi ve toksik olup olmadıklarının mutlaka araştırılması gerekmektedir. İlaç tasarımında, daha etkin, toksisitesi azaltılmış, daha güvenli bileşiklere veya dağılım, absorbsiyon sorunları düzeltilmiş ilaçlara ulaşmak için önemli ipuçları sağlaması ilaç metabolizması çalışmalarını güncel kılmaktadır. Bu derleme ile metabolizma kavramına değinilmiş, metabolizmanın önemi vurgulanmış ve ilaç metabolizması çalışmalarından örnekler verilmiştir

References

  • 1. Kayaalp O. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji 2009. Cilt 1, pp. 40-52. Pelikan Yayıncılık Ltd. Lti., Ankara
  • 2. Akgün H, Balkan A, Bilgin AA, Çalış Ü, Gökhan N, Dalkara S, Erdoğan H, Erol DD, Ertan M, Özkanlı F, Palaska E, Saraç S, Şafak C, Tozkoparan B. Farmasötik Kimya 2004. pp. 109- 148. Hacettepe Yayınları, Ankara.
  • 3. Rollas S. İlaç Metabolizması (Biyotransformasyon) 1992. Marmara Üniversitesi Yayın No: 525, Eczacılık Fakültesi Yayın No: 10, İstanbul.
  • 4. Brunton LL, Lazo JS, Parker KL. Goodman&Gilman Tedavinin Farmakolojik Temeli 2009. pp. 71-93. Nobel Tıp Kitabevleri, İstanbul.
  • 5. Parkinson A. Biotransformation of Xenobiotics 2001. Chapter 6. McGraw-Hill.
  • 6. Kaymaz S. İndol-3-karbinol’ün in vitro mikrozomal metabolik reaksiyonlarının incelenmesi 2006. Yüksek lisans tezi. Marmara Üniversitesi, İstanbul.
  • 7. Black JL, O’Kane DJ, Mrazek DA. The impact of CYP allelic variation on antidepressant metabolism: a review. Expert Opin Drug Metab Toxicol 2007; 3(1): 21-31.
  • 8. Yang L, Li Y, Hong H, Chang CW, Guo LW, Lyn-Cook B, Shi L, Ning B. Sex Differences in the Expression of Drug-Metabolizing and Transporter Genes in Human Liver. J Drug Metab Toxicol 2012; 3(3): e111.
  • 9. Sun J, Schnackenberg LK, Holland RD, Schmitt TC, Cantor GH. Metabonomics evaluation of urine from rats given acute and chronic doses of acetaminophen using NMR and UPLC/MS. J. Chromatogr B. Analyt Technol Biomed Life Sci 2008; 871: 328-40.
  • 10. Plumb RS, Granger JH, Stumpf CL, Johnson KA, Smith BW. A rapid screening approach to metabonomics using UPLC and oa-TOF mass spectrometry: application to age, gender and diumal variation in normal/Zucker obese rats and black, white and nude mice. Analyst 2005; 130: 844-49.
  • 11. Drug metabolism. http://en.wikipedia.org/wiki/Drug_metabolism. (Son erişim tarihi: 13.06.2014
  • 12. Fura A. Role of pharmacologically active metabolites in drug discovery and development. Drug Disc Today 2006; 11: 133-142.
  • 13. Kaplan JP, Raizon BM. New Anticonvulsants: Schiff Bases of-aminobutyric Acid and gammaaminobutyramide. J Med Chem 1980; 23: 702-04.
  • 14. Johno I, Kudwick BT, Levy RH. Pharmacokinetic Profile of Progabide, a New gamma -Aminobutyric Acid-Mimetic Drug, in Rhesus Monkey. J Pharm Sci 1982; 71: 633-6.
  • 15. Bergmann KJ. Progabide: A New GABAMimetic Agents in Clinical Use Clin Neuropharmacol 1985; 8: 13-26.
  • 16. Das N, Dhanawat M, Dash B, Nagarwal RC, Shrivastava SK. Codrug: An efficient approach for drug optimization. Eur J Pharm Sci 2010; 41: 571-588.
  • 17. Aynacıoğlu AŞ. Psikiyatrik Hastalıkların İlaçlarla Tedavisinde Farmakogenetiğin Önemi. Klinik Psikiyatri 2001; 4: 249-52.
  • 18. Ülgen M. In vitro oksidatif mikrozamal 1. faz ilaç metabolizması teknikleri. J Pharm Univ Marm 1993; 9: 165.
  • 19.Çakmak A. Bazı substitüe alifatik-aromatik amidlerin ve hidroksamik asitlerin in vitro mikrozomal metabolizmaları 2007. Yüksek lisans tezi. Marmara Üniversitesi, İstanbul.
  • 20.Blake TJ. Structure elucidation of drug metabolites using thermospray liquid chromatography-mass spectrometry. J Chromatogr 1987; 394(1): 171-81.
  • 21. Heitmeier S, Blaschke G. Direct determination of drug metabolites in body fluids by capillary electrophoresis, e.g. non-opioid analgetics. Pharmazie 1996; 25(5): 276.
  • 22. Tozuka Z, Kaneko H, Shiraga T, Beppu M, Niwa, T, Kawamura A, Kagayama A. New SRM Data Dependent Exclusion (MS)n Measurement for Structural Determination of Drug Metabolites Using LC/ ESI/ Ion Trap MS. Drug Metab Pharmacokin 2003; 18 (6): 390-403.
  • 23. Ülgen M. Yüksek Basınçlı Sıvı Kromatografisinin İlaç Metabolizması Çalışmalarına Uygulanması, HPLC Tekniği ve Uygulamaları Kursu, 11-15 Haziran 2007, Malatya.
  • 24. Lee MS, Yost RA, Perchalski RJ. Chapter 30. Tandem Mass Spectrometry for the Identification of Drug Metabolites. Ann Rep Med Chem 1986; 21: 313-21.
  • 25. Grunwald H, Hargreaves P, Gebhardt K, Klauer D, Serafyn A, Hoffmann AS, Schleimer M, Schlotterbeck G, Wind M. Experiments for a systematic comparison between stable-isotope- (deuterium) labeling and radio-(14C) labeling fort he elucidation of the in vitro metabolic pattern of pharmaceutical drugs. J Pharm Biomed Anal 2013; 85: 138-44.
  • 26. Schaut A, De Saeger S, Sergent T, Schneider YJ, Larondelle Y, Pussemier L, Blank R, Van Peteghem C. Chromatographic methods for biotransformation studies of ochratoxin A Biomed Chromatogr 2008; 22: 1013–20.
  • 27.Barrera B, Lobato LG, Otero JA, Real R, Prieto JG, Álvarez AI, Merino G. Effects of triclabendazole on secretion of danofloxacin and moxidectin into the milk of sheep: Role of triclabendazole metabolites as inhibitors of the ruminant ABCG2 transporter. Vet.2013;http://dx.doi.org/j.tvjl.2013.07.033
  • 28. Oruç EE, Koçyiğit-Kaymakcioglu B, YılmazDemircan F, Gürbüz Y, Kalaca S, Küçükgüzel SG, Ülgen M, Rollas S. An high-performance liquid chromatographic method for the quantification of cotinine in the urine of preschool children. Pharmazie 2006; 61(10): 823-27.
  • 29. Yılmaz F, Aricioğlu-Kartal F, Ülgen M, Gorrod JW. In vitro mircosomal metabolism of N-benzyl and N-benzoylnornicotine derivates by rat. Eur J Drug Metab Pharmacokinet 2004; 29(4): 249-56.
  • 30.Bekce B, Sener G, Oktav M, Ülgen M, Rollas S. In vitro and in vivo metabolism of ethyl 4-((2- hydroxy-1-naphthyl)azo)benzoate. Eur J Drug Metab Pharmacokinet 2005; 30(1-2): 91-7.
  • 31.Bulut G, Oktav M, Ülgen M. The stability studies and in vitro hepatic microsomal metabolism of some α-phenyl-N-substituted nitrones in rats. Eur J Drug Metab Pharmacokinet 2004; 29(4): 237-48.

Drug Metabolism and Its Importance in Pharmaceutical Chemistry

Year 2016, Volume: 5 Issue: 2, 35 - 46, 01.10.2016

Abstract

Being modified of drugs to generally more polar new compounds by chemical transformation via enzymes which are in organism is called biotransformation or metabolism. By metabolism, drugs and other foreign substances which are taken into body are converted to less toxic form and excreted from the body as soon as possible by making polar. Otherwise, the effects of some drugs are seen due to the pharmacological effects of their metabolits which are formed by metabolism. Isolation of metabolits and to investigate whether they are toxic or not is necessary in order to enter the market of a drug. In drug design, providing important clues to reach compounds which are more efficient, reduced toxicity, safer or drugs whose dispersion and absorption problems are eliminated makes drug metabolism studies current. In this review, it is referred to the concept of metabolism, is emphasized the importance of metabolism andexamples of drug metabolism studies are given

References

  • 1. Kayaalp O. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji 2009. Cilt 1, pp. 40-52. Pelikan Yayıncılık Ltd. Lti., Ankara
  • 2. Akgün H, Balkan A, Bilgin AA, Çalış Ü, Gökhan N, Dalkara S, Erdoğan H, Erol DD, Ertan M, Özkanlı F, Palaska E, Saraç S, Şafak C, Tozkoparan B. Farmasötik Kimya 2004. pp. 109- 148. Hacettepe Yayınları, Ankara.
  • 3. Rollas S. İlaç Metabolizması (Biyotransformasyon) 1992. Marmara Üniversitesi Yayın No: 525, Eczacılık Fakültesi Yayın No: 10, İstanbul.
  • 4. Brunton LL, Lazo JS, Parker KL. Goodman&Gilman Tedavinin Farmakolojik Temeli 2009. pp. 71-93. Nobel Tıp Kitabevleri, İstanbul.
  • 5. Parkinson A. Biotransformation of Xenobiotics 2001. Chapter 6. McGraw-Hill.
  • 6. Kaymaz S. İndol-3-karbinol’ün in vitro mikrozomal metabolik reaksiyonlarının incelenmesi 2006. Yüksek lisans tezi. Marmara Üniversitesi, İstanbul.
  • 7. Black JL, O’Kane DJ, Mrazek DA. The impact of CYP allelic variation on antidepressant metabolism: a review. Expert Opin Drug Metab Toxicol 2007; 3(1): 21-31.
  • 8. Yang L, Li Y, Hong H, Chang CW, Guo LW, Lyn-Cook B, Shi L, Ning B. Sex Differences in the Expression of Drug-Metabolizing and Transporter Genes in Human Liver. J Drug Metab Toxicol 2012; 3(3): e111.
  • 9. Sun J, Schnackenberg LK, Holland RD, Schmitt TC, Cantor GH. Metabonomics evaluation of urine from rats given acute and chronic doses of acetaminophen using NMR and UPLC/MS. J. Chromatogr B. Analyt Technol Biomed Life Sci 2008; 871: 328-40.
  • 10. Plumb RS, Granger JH, Stumpf CL, Johnson KA, Smith BW. A rapid screening approach to metabonomics using UPLC and oa-TOF mass spectrometry: application to age, gender and diumal variation in normal/Zucker obese rats and black, white and nude mice. Analyst 2005; 130: 844-49.
  • 11. Drug metabolism. http://en.wikipedia.org/wiki/Drug_metabolism. (Son erişim tarihi: 13.06.2014
  • 12. Fura A. Role of pharmacologically active metabolites in drug discovery and development. Drug Disc Today 2006; 11: 133-142.
  • 13. Kaplan JP, Raizon BM. New Anticonvulsants: Schiff Bases of-aminobutyric Acid and gammaaminobutyramide. J Med Chem 1980; 23: 702-04.
  • 14. Johno I, Kudwick BT, Levy RH. Pharmacokinetic Profile of Progabide, a New gamma -Aminobutyric Acid-Mimetic Drug, in Rhesus Monkey. J Pharm Sci 1982; 71: 633-6.
  • 15. Bergmann KJ. Progabide: A New GABAMimetic Agents in Clinical Use Clin Neuropharmacol 1985; 8: 13-26.
  • 16. Das N, Dhanawat M, Dash B, Nagarwal RC, Shrivastava SK. Codrug: An efficient approach for drug optimization. Eur J Pharm Sci 2010; 41: 571-588.
  • 17. Aynacıoğlu AŞ. Psikiyatrik Hastalıkların İlaçlarla Tedavisinde Farmakogenetiğin Önemi. Klinik Psikiyatri 2001; 4: 249-52.
  • 18. Ülgen M. In vitro oksidatif mikrozamal 1. faz ilaç metabolizması teknikleri. J Pharm Univ Marm 1993; 9: 165.
  • 19.Çakmak A. Bazı substitüe alifatik-aromatik amidlerin ve hidroksamik asitlerin in vitro mikrozomal metabolizmaları 2007. Yüksek lisans tezi. Marmara Üniversitesi, İstanbul.
  • 20.Blake TJ. Structure elucidation of drug metabolites using thermospray liquid chromatography-mass spectrometry. J Chromatogr 1987; 394(1): 171-81.
  • 21. Heitmeier S, Blaschke G. Direct determination of drug metabolites in body fluids by capillary electrophoresis, e.g. non-opioid analgetics. Pharmazie 1996; 25(5): 276.
  • 22. Tozuka Z, Kaneko H, Shiraga T, Beppu M, Niwa, T, Kawamura A, Kagayama A. New SRM Data Dependent Exclusion (MS)n Measurement for Structural Determination of Drug Metabolites Using LC/ ESI/ Ion Trap MS. Drug Metab Pharmacokin 2003; 18 (6): 390-403.
  • 23. Ülgen M. Yüksek Basınçlı Sıvı Kromatografisinin İlaç Metabolizması Çalışmalarına Uygulanması, HPLC Tekniği ve Uygulamaları Kursu, 11-15 Haziran 2007, Malatya.
  • 24. Lee MS, Yost RA, Perchalski RJ. Chapter 30. Tandem Mass Spectrometry for the Identification of Drug Metabolites. Ann Rep Med Chem 1986; 21: 313-21.
  • 25. Grunwald H, Hargreaves P, Gebhardt K, Klauer D, Serafyn A, Hoffmann AS, Schleimer M, Schlotterbeck G, Wind M. Experiments for a systematic comparison between stable-isotope- (deuterium) labeling and radio-(14C) labeling fort he elucidation of the in vitro metabolic pattern of pharmaceutical drugs. J Pharm Biomed Anal 2013; 85: 138-44.
  • 26. Schaut A, De Saeger S, Sergent T, Schneider YJ, Larondelle Y, Pussemier L, Blank R, Van Peteghem C. Chromatographic methods for biotransformation studies of ochratoxin A Biomed Chromatogr 2008; 22: 1013–20.
  • 27.Barrera B, Lobato LG, Otero JA, Real R, Prieto JG, Álvarez AI, Merino G. Effects of triclabendazole on secretion of danofloxacin and moxidectin into the milk of sheep: Role of triclabendazole metabolites as inhibitors of the ruminant ABCG2 transporter. Vet.2013;http://dx.doi.org/j.tvjl.2013.07.033
  • 28. Oruç EE, Koçyiğit-Kaymakcioglu B, YılmazDemircan F, Gürbüz Y, Kalaca S, Küçükgüzel SG, Ülgen M, Rollas S. An high-performance liquid chromatographic method for the quantification of cotinine in the urine of preschool children. Pharmazie 2006; 61(10): 823-27.
  • 29. Yılmaz F, Aricioğlu-Kartal F, Ülgen M, Gorrod JW. In vitro mircosomal metabolism of N-benzyl and N-benzoylnornicotine derivates by rat. Eur J Drug Metab Pharmacokinet 2004; 29(4): 249-56.
  • 30.Bekce B, Sener G, Oktav M, Ülgen M, Rollas S. In vitro and in vivo metabolism of ethyl 4-((2- hydroxy-1-naphthyl)azo)benzoate. Eur J Drug Metab Pharmacokinet 2005; 30(1-2): 91-7.
  • 31.Bulut G, Oktav M, Ülgen M. The stability studies and in vitro hepatic microsomal metabolism of some α-phenyl-N-substituted nitrones in rats. Eur J Drug Metab Pharmacokinet 2004; 29(4): 237-48.
There are 31 citations in total.

Details

Primary Language Turkish
Journal Section Collection
Authors

Zeynep Özdemir This is me

Arzu Karakurt This is me

Publication Date October 1, 2016
Published in Issue Year 2016 Volume: 5 Issue: 2

Cite

APA Özdemir, Z., & Karakurt, A. (2016). İlaç Metabolizması ve Farmasötik Kimyada Önemi. Annals of Health Sciences Research, 5(2), 35-46.
AMA Özdemir Z, Karakurt A. İlaç Metabolizması ve Farmasötik Kimyada Önemi. Ann Health Sci Res. October 2016;5(2):35-46.
Chicago Özdemir, Zeynep, and Arzu Karakurt. “İlaç Metabolizması Ve Farmasötik Kimyada Önemi”. Annals of Health Sciences Research 5, no. 2 (October 2016): 35-46.
EndNote Özdemir Z, Karakurt A (October 1, 2016) İlaç Metabolizması ve Farmasötik Kimyada Önemi. Annals of Health Sciences Research 5 2 35–46.
IEEE Z. Özdemir and A. Karakurt, “İlaç Metabolizması ve Farmasötik Kimyada Önemi”, Ann Health Sci Res, vol. 5, no. 2, pp. 35–46, 2016.
ISNAD Özdemir, Zeynep - Karakurt, Arzu. “İlaç Metabolizması Ve Farmasötik Kimyada Önemi”. Annals of Health Sciences Research 5/2 (October 2016), 35-46.
JAMA Özdemir Z, Karakurt A. İlaç Metabolizması ve Farmasötik Kimyada Önemi. Ann Health Sci Res. 2016;5:35–46.
MLA Özdemir, Zeynep and Arzu Karakurt. “İlaç Metabolizması Ve Farmasötik Kimyada Önemi”. Annals of Health Sciences Research, vol. 5, no. 2, 2016, pp. 35-46.
Vancouver Özdemir Z, Karakurt A. İlaç Metabolizması ve Farmasötik Kimyada Önemi. Ann Health Sci Res. 2016;5(2):35-46.