Metabolic stability and determination of cytochrome P450 isoenzymes' contribution to the metabolism of medetomidine in dog liver microsomes

Biomedical Chromatography

Volumn 24, Issue 8, 2010, Pages 868-877

  Duhamel, Marie Claude ^a   Troncy, Éric ^a   Beaudry, Francis ^a  

^a UNIVERSITÉ DE MONTRÉAL   (Canada)

Author keywords

Cytochrome P450; In vitro metabolism; Mass spectrometry; Medetomidine; Metabolic stability; Microsomes

Indexed keywords

ACETONE; ANIMALS; ENZYMES; MASS SPECTROMETRY; PHARMACOKINETICS; PHYSIOLOGY; STABILITY;

ADRENERGIC RECEPTORS; CYTOCHROMES P450; IN VITRO METABOLISM; IN-VITRO; IN-VIVO; LIVER MICROSOMES; MEDETOMIDINE; METABOLIC STABILITY; MICROSOME; NON LINEAR;

METABOLISM;

CHLORAMPHENICOL; CHLORZOXAZONE; CYTOCHROME P450; CYTOCHROME P450 2D; CYTOCHROME P450 2E1; CYTOCHROME P450 3A; DEXTROMETHORPHAN; FENTANYL; ISOENZYME; KETAMINE; KETOCONAZOLE; MEDETOMIDINE; MIDAZOLAM; QUINIDINE; ALPHA ADRENERGIC RECEPTOR STIMULATING AGENT;

ANIMAL TISSUE; ARTICLE; COMPETITIVE INHIBITION; DOG; DRUG CLEARANCE; DRUG METABOLISM; ELECTROSPRAY MASS SPECTROMETRY; ENZYME ACTIVITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; LIQUID CHROMATOGRAPHY; LIVER MICROSOME; MASS SPECTROMETRY; MICHAELIS MENTEN KINETICS; NONHUMAN; PH; PREMEDICATION; STANDARD; ANIMAL; CHEMISTRY; ENZYMOLOGY; KINETICS; METABOLISM;

ANIMALIA; CANIS FAMILIARIS;

ADRENERGIC ALPHA-AGONISTS; ANIMALS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CYTOCHROME P-450 ENZYME SYSTEM; DOGS; ISOENZYMES; KINETICS; MEDETOMIDINE; MICROSOMES, LIVER;

EID: 77954726205     PISSN: 02693879     EISSN: 10990801     Source Type: Journal    
DOI: 10.1002/bmc.1379     Document Type: Article

References (40)

1. Armstrong SC, Wynn GH and Sandson NB. Pharmacokinetic drug interactions of synthetic opiate analgesics. Psychosomatics 2009; 50(2): 169-176.
2. Avsaroglu H, Bull S, Maas-Bakker RF, Scherpenisse P, van Lith HA, Bergwerff AA, Hellebrekers LJ, Van Zutphen LFM and Fink-Gremmels J. Differences in hepatic cytochrome P450 activity correlate with the strain-specific biotransformation of medetomidine in AX/JU and IIIVO /JU inbred rabbits. Journal of Veterinary Pharmacology and Therapeutics 2008; 31: 368-377.
3. Beaudry F. Statistical evaluation of linearity and non linearity of LC-MS/ MS quantitation analysis. Pharmaceutical Science 1999; 1(4): 2437.
4. Beaudry F, Le Blanc JCY, Coutu M, Ramier I, Moreau JP and Brown NK Metabolite profiling study of propranolol in rat using LC/MS/MS analysis. Biomedical Chromatography 1999; 13(5): 363-369.
5. Bergstrom K. Cardiovascular and pulmonary effects of a new sedative/ analgesic (medetomidine) as a preanaesthetic drug in the dog. Acta Veterinaria Scandinavica 1988; 29: 109-116.
6. Center for Drug Evaluation and Research and Center for Veterinary Medicine. Guidance for Industry. Bioanalytical Method Validation; http:// www.fda.gov/cder/guidance/4252fnl.pdf, May 2001.
7. Chanda S, Bashir M, Babbar S, Koganti A and Bley K. In vitro hepatic and skin metabolism of capsaicin. Drug Metabolism and Disposition 2008; 36(4): 670-675. (Pubitemid 351468372)
8. Cormack JR, Orme RM and Costello TG. The role of alpha2-agonists in neurosurgery. Journal of Clinical Neuroscience 2005; 12(4): 375-378.
9. Court MH, Von Moltke LL, Shader RI and Greenblatt DJ. Biotransformation of chlorzoxazone by hepatic microsomes from humans and ten other mammalian species. Biopharmaceutical Drug Disposition 1997; 18: 213-226.
10. Crassous PA, Denis C, Paris H and Sénard JM. Interest of alpha2-adrenergic agonists and antagonists in clinical practice: background, facts and perspectives. Current Topics in Medicinal Chemistry 2007; 7(2): 187-194. (Pubitemid 46062389)
11. Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clinical Pharmacokinetic 2007; 38(1): 41-57.
12. Ethier MR, Mathews KA, Valverde A, Kerr C, Bersenas AM, Nykamp SG and Davis C. Evaluation of the efficacy and safety for use of two sedation and analgesia protocols to facilitate assisted ventilation of healthy dogs. American Journal of Veterinary Research 2008; 69(10): 1351-1359.
13. Gómez-Villamandos RJ, Palacios C, Benítez A, Granados MM, Domínguez JM, López I, Ruiz I, Aguilera E and Santisteban JM. Dexmedetomidine or medetomidine premedication before propofol-desflurane anaesthesia in dogs. Journal of Veterinary Pharmacology and Therapeutics 2006; 29(3): 157-163.
14. Ha-Duong NT, Dijols S, Macherey AC, Goldstein JA, Dansette PM and Mansuy D. Ticlopidine as a selective mechanism-based inhibitor of human cytochrome P450 2C19. Biochemistry 2001; 40(40): 12112-12122. (Pubitemid 32946552)
15. Hay Kraus BL, Greenblatt DJ, Venkatakrishnan K and Court MH. Evidence for propofol hydroxylation by cytochrome P4502B11 in canine liver microsomes: breed and gender differences. Xenobiotica 2000; 30(6): 575-588. (Pubitemid 30449568)
16. Hellebrekers LJ and Sap R. Medetomidine as a premedicant for ketamine, propofol or fentanyl anaesthesia in dogs. Veterinary Record 1997; 140: 545-548. (Pubitemid 27232267)
17. Hopfgartner G and Bourgogne E. Quantitative high-throughput analysis of drugs in biological matrices by mass spectrometry. Mass Spectrometry Review 2003; 22(3): 195-214.
18. Jang GR, Harris RZ and Lau DT. Pharmacokinetics and its role in small molecule drug discovery research. Medical Research Review 2001; 21(5): 382-396. (Pubitemid 32751461)
19. Kaartinen M J, Pang DSJ, Moreau M, Vainio O, Beaudry F, del Castillo JRE, Cuvelliez SG, Troncy E. Hemodynamic response to an intravenous infusion of medetomidine at six different dose regimens in isoflurane-anesthetized dogs. Veterinary Therapeutics 2009, in press.
20. Ko JC, Payton M, Weil AB, Kitao T and Haydon T. Comparison of anesthetic and cardiorespiratory effects of tiletamine-zolazepam-butorphanol and tiletamine-zolazepam-butorphanol-medetomidine in dogs. Veterinary Therapeutics 2007; 8(2): 113-126. (Pubitemid 351419314)
21. Kostiainen R, Kotiaho T, Kuuranne T and Auriola S. Liquid chromatography/ atmospheric pressure ionization-mass spectrometry in drug metabolism studies. Journal of Mass Spectrometry 2003; 38: 357-372. (Pubitemid 36582213)
22. Kuroha M, Azumano A, Kuze Y, Shimoda M and Kokue E. Effect of multiple dosing of ketoconazole on pharmacokinetics of midazolam, a cytochrome P-450 3A substrate in beagle dogs. Drug Metababolism and Disposition 2002; 30(1): 63-68. (Pubitemid 34016942)
23. Lash LH. Drug Metabolism and Transport. Humana: Totawa, NJ, 2004.
24. Masimirembwa CM, Thompson R, Andersson TB. In vitro high throughput of compounds for favorable metabolic properties in drug discovery. Combinatorial Chemistry & High Throughput Screening 2001; 245-263. (Pubitemid 32433637)
25. Michaelis L and Menten ML. Die Kinetik der invertinwirkung. Biochemische Zeitschrift 1913; 49: 33-369 (in German).
26. Obach RS, Baxter JG, Liston TE, Silber BM, Jones BC, MacIntyre F, Rance DJ and Wastall P. The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. Journal of Pharmacology and Experimental Therapeutics 1997; 283(1):46-58.
27. Obach RS. Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes. Drug Metababolism and Disposition 1999; 27(11): 1350-1359.
28. Paulson SK, Engel L, Reitz B, Bolten S, Burton EG, Maziasz TJ, Yan B and Schoenhard GL. Evidence for polymorphism in the canine metabolism of the cyclooxygenase 2 inhibitor, celecoxib. Drug Metababolism and Disposition 1999; 27(10): 1133-1142.
29. Pypendopn BH, Verstegen JP. Hemodynamic effects of medetomidine in the dog: a dose titration study. Veterinary Surgery 1998; 27: 612-622.
30. Ranheim B, Søli NE, Ryeng KA, Arnemo JM and Horsberg TE. Pharmacokinetics of medetomidine and atipamezole in dairy calves: an agonist-antagonist interaction. Journal of Veterinary Pharmacology and Therapeutics 1998; 21: 428-432. (Pubitemid 29022747)
31. Rodrigues AD and Roberts EM. The in vitro interaction of dexmedetomidine with human liver microsomal cytochrome P4502D6 (CYP2D6). Drug Metababolism and Disposition 1997; 25(5): 651-655.
32. Salonen JS. Pharmacokinetics of medetomidine. Acta Veterinaria Scandinavica Supplements 1989; 85: 49-54.
33. Segal I. Enzyme Kinetics: Behaviour and Analysis of Rapid Equilibrium and Steady-State Enzyme. John Wiley & Sons: New York, NY, 1975.
34. Shargel L, Wu-Pong S and Yu ABC. Applied Biopharmaceutics and Pharmacokinetics, 5th edn. McGraw-Hill: New York, 2005.
35. Sinclair MD. A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice. The Canadian Veterinary Journal 2003; 44(11): 885-897.
36. Smith DA, Jones BC and Walker DK. Design of drugs involving the concepts and theories of drug metabolism and pharmacokinetics. Medical Research Review 1996; 16(3): 243-266. (Pubitemid 26146807)
37. Stone LS, Kitto KF, Eisenach JC, Fairbanks CA and Wilcox GL. ST91 [2-(2,6-diethylphenylamino)-2-imidazoline hydrochloride]-mediated spinal antinociception and synergy with opioids persists in the absence of functional alpha-2A- or alpha-2C-adrenergic receptors. Journal of Pharmacology and Experimental Therapeutic 2004; 323(3): 899-906.
38. Thummela KE, Kunzea KL and Shen DD. Enzyme-catalyzed processes of first-pass hepatic and intestinal drug extraction. Advanced Drug Delivery Review 1997; 27: 99-127.
39. Toutain PL, Bousquet-Mélou A. Plasma clearance. Journal of Veterinary Pharmacology and Therapeutics 2004; 27: 415-425.
40. Verstegen J and Petcho A. Medetomidine-butorphanol-midazolam for anaesthesia in dogs and its reversal by atipamezole. Veterinary Record 1993; 132(14): 353-357. (Pubitemid 23108372)