Porovnanie metabolického pomeru metoprolol/α-hydroxymetoprolol po jednorázovom a opakovanom užití
Authors:
J. Ďuricová; I. Peřinová; I. Kacířová; M. Grundmann
Authors‘ workplace:
Department of Clinical Pharmacology, University Hospital Ostrava, and Faculty of Medicine, University of Ostrava, Czech Republic
Published in:
Čes. slov. Farm., 2010; 59, 222-226
Category:
Original Articles
Overview
Metabolický pomer (MR) metoprololu/α-hydroxymetoprololu za 3 hod po užití jednorázovej dávky metoprololu sa používa na stanovenie fenotypu enzýmu cytochrómu P450 2D6. Cieľom tejto práce bolo porovnať metabolickú aktivitu cytochrómu P450 2D6 po prvom a opakovanom užití metoprololu. Do tejto práce bolo zahrnutých 13 pacientov s hypertenziou (7 žien), u ktorých bolo plánované nasadenie beta-blokátora metoprololu. Vek (priemer ± SD) bol 42,8 ± 12,9 rokov, telesná hmotnosť (priemer ± SD) bola 94,0 ± 25,4 kg. Dávka metoprololu bola u každého pacienta zvolená na základe klinického stavu pacienta v deň užitia prvej tablety. Krvné odbery boli urobené po užití prvej dávky metoprololu a najmenej 2 týždne od nasadenia metoprololu k zaručeniu ustáleného stavu (opakované užívanie). Na základe hodnôt MR boli všetci pacienti po jednorázovom i opakovanom užití zaradení do tej istej fenotypovej skupiny. Pozorovali sme tesnú koreláciu medzi MR po jednorázovom a opakovanom užití metoprololu (rs = 0,8418, P = 0,0003). Všetci pacienti boli v oboch odberoch zaradení do rovnakej fenotypovej skupiny, extenzivný metabolizátor i napriek signifikantnému rozdielu medzi MR metoprololu/α-hydroxymetoprololu po jednorázovom a opakovanom užití (medián 0,59 vs. 0,81, P = 0,0266), Využitie MR metoprololu/α‑hydroxymetoprololu u pacientov na dlhodobej terapii metoprololom je vhodné pre stanovenie fenotypu enzýmu cytochrómu P450 2D6.
Kľúčové slová:
cytochróm P450 2D6 – fenotyp – substrátová látka – metoprolol
Sources
1. Duricova, J., Grundmann, M.: CYP2D6 a jeho klinický význam. Klin. Farmakol. Farm., 2007; 21, 80–83.
2. Anzenbacher, P., Anzenbacherova, E.: Cytochrome P450 and metabolism of xenobiotics. Cell. Mol. Life Sci., 2001; 58, 737–747.
3. Home page of the human cytochrome P450 (CYP 2D6) allele nomenclature [updated 2010 July 20]. Available from: http://www.cypalleles.ki.se/cyp2d6.htm
4. Aklillu, E., Herrlin, K., Gustafsson, L. L., Bertilsson, L., Ingelman-Sundberg, M.: Evidence for environmental influence on CYP2D6-catalysed debrisoquine hydroxylation as demonstrated by phenotyping and genotyping of Ethiopians living or in Sweden. Pharmacogenetics, 2002; 12, 375–383.
5. Thürmann, P. A., Haack, S., Werner, U., Szymanski, J., Haase, G., Drewelow, B., Reimann, I. R., Hippius, M., Siegmund, W., May, K., Hasford, J.: Tolerability of ß-blockers metabolized via cytochrome P450 2D6 is sex-dependent. Clin. Pharmacol. Ther., 2006; 80, 551–553.
6. Villeneuve, J.P., Pichette, V.: Cytochrome P450 and liver diseases. Curr. Drug. Metab., 2004; 5, 273–282.
7. Wadelius, M., Darj, E., Frenne, G., Rane, A.: Induction of CYP2D6 in pregnancy. Clin. Pharmacol. Ther., 1997; 62, 400–407.
8. Nekvindova, J., Anzenbacher, P.: Interactions of food and dietary supplements with drug metabolising cytochrome P450 enzymes. Čes. slov. Farm., 2007; 56, 165–173.
9. Zourkova, A., Hadasova, E.: Paroxetine-induced conversion of cytochrome P450 2D6 phenotype and occurence of adverse effects. Gen. Physiol. Biophys., 2003; 22, 103–113.
10. Labbé, L, O’Hara, G, Lefebvre, M, Lessard, E, Gilbert, M, Adedoyin, A., Champagne, J., Hamelin, B., Turgeon, J.: Pharmacokinetic and pharmacodynamic interaction between mexiletine and propafenone in human beings. Clin. Pharmacol. Ther., 2000; 67, 44–57.
11. Grundmann, M., Duricova, J., Perinova, I., Kacirova, I., Jeziskova, I., Jurckova, N.: Influence of propafenone on enzymatic activity of P4502D6 in a patient on long therapy with metoprolol. Basic. Clin. Pharmacol. Toxicol., 2009; 105(Suppl 1), 44.
12. Frye, R. F.: Probing the world of cytochrome P450 enzymes. Mol. Interv., 2004; 4, 157–162.
13. Zanger, U. M., Raimundo, S., Eichelbaum, M.: Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch. Pharmacol., 2004; 369, 23–37.
14. Frank, D., Jaehde, U., Fuhr, U.: Evaluation of probe drugs and pharmacokinetic metrics for CYP2D6 phenotyping. Eur. J. Clin. Pharmacol., 2007; 63, 321–333.
15. Sohn, D. R., Kusaka, M., Shin, S. G., Jang, I. J., Chiba, K., Ishizaki, T.: Utility of a one-point (3-hour postdose) plasma metabolic ratio as a phenotyping test using metoprolol in two East Asian populations. Ther. Drug. Monit., 1992; 14, 184–189.
16. RegĆrdh, C. G., Johnsson, G.: Clinical pharmacokinetics of metoprolol. Clin. Pharmacokinet., 1980; 5, 557–569.
17. Brosen, K., Gram, L. F.: Clinical significance of the sparteine/debrisoquine oxidation polymorphism. Eur. J. Clin. Pharmacol., 1989; 36, 537–547.
18. Perinova, I., Duricova, J., Brozmanova, H., Kacirova, I., Grundmann, M.: Determination of metoprolol and its metabolite α-hydroxymetabolite in serum by HPLC method with fluorescence detection. Ceska. slov. Farm., 2008; 57, 254–259
19. Jonkers, R. E., Koopmans, R. P., Portier, E. J. G., van Boxtel, Ch. J.: Debrisoquine phenotype and the pharmacokinetics and beta-2-receptor pharmacodynamics of metoprolol and its enantiomers. J. Pharmacol. Experimental. Ther., 1990; 256, 959–966.
20. Tamminga, W. J., Wemer, J., Oosterhuis, B., Brakenhoff, J. P. G., Gerrits, M. G. F., de Zeeuw, R. A. de Leij, L. F. M. H., Jonkman, J. H. G.: An optimized methodology for combined phenotyping and genotyping on CYP2D6 and CYP2C19. Eur. J. Clin. Pharmacol., 2001; 57, 143–146.
21. Goryachkina, K., Burbello, A., Boldueva, S., Babak, S., Bergman, U., Bertilsson, L.: CYP2D6 is a major determinant of metoprolol disposition and effects in hospitalized Russian patients treated for acute myocardial infarction. Eur. J. Pharmacol., 2008; 64, 1163–1173.
22. Goryachkina, K., Burbello, A., Boldueva, S., Babak, S., Bergman, U, Bertilsson, L.: Inhibition of metoprolol metabolism and potentiation of its effects by paroxetine in routinely treated patients with acute myocardial infarction (AMI). Eur. J. Clin. Pharmacol., 2008; 64, 275–282.
23. Ismail, R., The, L. K.: The relevance of the CYP2D6 genetic polymorphism on chronic metoprolol therapy in cardiovascular patients. J. Clin. Pharm. Ther., 2006; 31, 99–109.
24. Rau, T., Heide, R., Bergmann, K., Wuttke, H., Werner, U., Feifel, N., Eschenhagen, T.: Effect of the CYP2D6 genotype on metoprolol metabolism persists during long-term treatment. Pharmacogenetics, 2002; 12, 165–172.
25. Roh, H. K., Chung, J. Y., Oh, D. Y., Park, Ch. S., Svensson, J. O., Dahl M. L., Bertilsson L.: Plasma concentrations of haloperidol are related to CYP2D6 genotype at low, but not high doses of haloperidol in Korean schizophrenic patients. Br. J. Clin. Pharmacol., 2001; 52, 265–271.
Labels
Pharmacy Clinical pharmacologyArticle was published in
Czech and Slovak Pharmacy
![Issue 5](https://www.prolekare.cz/media/cache/resolve/journal_issue/media/image_pdf/8a268c081ffdf2dc25ed1d7f2399fca1.jpeg)
2010 Issue 5
Most read in this issue
- Štúdium disolučných profilov tramadoliumchloridu z liekových foriem s riadeným uvoľňovaním matricového a zásobníkového typu
-
Léčivé přípravky v Obnoveném pražském dispensatoriu z roku 1750
I. část – úvod a prvních devět tříd lékových forem -
Obsahové látky
Philadelphus coronarius L. -
Léčivé přípravky v Obnoveném pražském dispensatoriu z roku 1750
II. část – zbylé lékové formy a vyhodnocení