Personalisierte Medizin in der Pharmakotherapie: Wie weit sind wir in der Veterinärmedizin?

Die personalisierte Medizin soll für jeden Patienten eine optimale Therapie ermöglichen. Dies erfordert, dass individuelle Unterschiede in der Arzneimittelantwort bekannt sind und vor Therapiebeginn auch diagnostisch bestimmt werden können. In der Veterinärmedizin ist dies aktuell nur in sehr wenigen Fällen (z. B. beim sog. MDR1-Defekt) möglich, in den nächsten Jahren werden aber große Fortschritte erwartet.

• Literatur

• 1 Mealey KL, Martinez SE, Villarino NF. et al. Personalized medicine: going to the dogs?. Human Genetics 2019; 138: 467-481
• 2 Fink-Gremmels J. Implications of hepatic cytochrome P450-related biotransformation processes in veterinary sciences. Eur J Pharmacol 2008; 585: 502-509
• 3 Kerb R. Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett 2006; 234: 4-33
• 4 Ma Q, Lu AYH. Pharmacogenetics, pharmacogenomics, and individualized medicine. Pharmacol Rev 2011; 63: 437-459
• 5 Ferraldeschi R, Newman WG. Pharmacogenetics and pharmacogenomics: a clinical reality. Ann Clin Biochem 2011; 48: 410-417
• 6 Fleischer S, Sharkey M, Mealey K. et al. Pharmacogenetic and metabolic differences between dog breeds: their impact on canine medicine and the use of the dog as a preclinical animal model. AAPS J 2008; 10: 110-119
• 7 Toutain PL, Ferran A, Bousquet-Melou A. Species differences in pharmacokinetics and pharmacodynamics. Handb Exp Pharmacol 2010; 199: 19-48
• 8 Kakehi M, Ikenaka Y, Nakayama SMM. et al. Uridine diphosphate-glucuronosyltransferase (UGT) xenobiotic metabolizing activity and genetic evolution in pinniped species. Toxicol Sci 2015; 147: 360369
• 9 Shrestha B, Reed JM, Starks PT. et al. Evolution of a major drug metabolizing enzyme defect in the domestic cat and other felidae: phylogenetic timing and the role of hypercarnivory. PLoS One 2011; 6 (03) e18046
• 10 Ramirez CJ, Minch JD, Gay JM. et al. Molecular genetic basis for fluoroquinolone-induced retinal degeneration in cats. Pharmacogenet Genomics 2011; 21: 66-75
• 11 Mise M, Hashizume T, Matsumoto S. et al. Identification of non-functional allelic variant of CYP1A2 in dogs. Pharmacogenetics 2004; 14: 769-773
• 12 Martinez SE, Andresen MC, Zhu Z. et al. Pharmacogenomics of poor drug metabolism in Greyhounds: Cytochrome P450 (CYP) 2B11 genetic variation, breed distribution, and functional characterization. Sci Rep 2020; 10: 69
• 13 Hay Kraus BL, Greenblatt DJ, Venkatakrishnan K. et al. Evidence for propofol hydroxylation by cytochrome P4502B11 in canine liver microsomes: breed and gender differences. Xenobiotica 2000; 30: 575-588
• 14 Martinez SE, Shi J, Zhu HJ. et al. Absolute quantitation of drug-metabolizing cytochrome P450 enzymes and accessory proteins in dog liver microsomes using label-free standard-free analysis reveals interbreed variability. Drug Metab Dispos 2019; 47: 1314-1324
• 15 Blaisdell J, Goldstein JA, Bai SA. Isolation of a new canine cytochrome P450 cDNA from the cytochrome P450 2C subfamily (CYP2C41) and evidence for polymorphic differences in its expression. Drug Metab Dispos 1998; 26: 278-283
• 16 Perez Jimenez TE, Mealey KL, Schnider D. et al. Identification of canine cytochrome P-450 s (CYPs) metabolizing the tramadol (+)-M1 and (+)-M2 metabolites to the tramadol (+)-M5 metabolite in dog liver microsomes. J Vet Pharmacol Ther 2018; 41: 815-824
• 17 Roussel F, Duignan DB, Lawton MP. et al. Expression and characterization of canine cytochrome P450 2D15. Arch Biochem Biophys 1998; 357: 27-36
• 18 Paulson SK, Engel L, Reitz B. et al. Evidence for polymorphism in the canine metabolism of the cyclooxygenase 2 inhibitor, celecoxib. Drug Metab Dispos 1999; 27: 1133-1142
• 19 Martinez MN, Antonovic L, Court M. et al. Challenges in exploring the cytochrome P450 system as a source of variation in canine drug pharmacokinetics. Drug Metab Rev 2013; 45: 218-230
• 20 Trepanier LA, Ray K, Winand NJ. et al. Cytosolic arylamine N-acetyltransferase (NAT) deficiency in the dog and other canids due to an absence of NAT genes. Biochem Pharmacol 1997; 54: 73-80
• 21 Mealey KL. Pharmacogenetics. Vet Clin North Am Small Anim Pract 2006; 36: 961-973
• 22 Geyer J, Janko C. Treatment of MDR1 mutant dogs with macrocyclic lactones. Curr Pharm Biotechnol 2012; 13: 969-986
• 23 Court MH, Greenblatt DJ. Molecular genetic basis for deficient acetaminophen glucuronidation by cats: UGT1A6 is a pseudogene, and evidence for reduced diversity of expressed hepatic UGT1A isoforms. Pharmacogenetics 2000; 10: 355-369
• 24 Graham MJ, Bell AR, Crewe HK. mRNA and protein expression of dog liver cytochromes P450 in relation to the metabolism of human CYP2C substrates. Xenobiotica 2003; 33: 225-237
• 25 Witherock VJ, Morgan DG, Lentz KA. et al. Phenacetin pharmacokinetics in CYP1A2-deficient beagle dogs. Drug Metab Dispos 2012; 40: 228-231
• 26 Aretz JS, Geyer J. Detection of the CYP1A2 1117C>T polymorphism in 14 dog breeds. J Vet Pharmacol Ther 2011; 34: 98-100
• 27 Aleman M, Nieto JE, Magdesian KG. Malignant hyperthermia associated with ryanodine receptor 1 (C7360 G) mutation in Quarter Horses. J Vet Intern Med 2009; 23: 329-334