Feline Drug Metabolism and Disposition: Pharmacokinetic Evidence for Species Differences and Molecular Mechanisms

Veterinary Clinics of North America - Small Animal Practice

Volumn 43, Issue 5, 2013, Pages 1039-1054

  Court, Michael H ^a  

^a WASHINGTON STATE UNIVERSITY   (United States)

Author keywords

Cat; Glucuronidation; Pharmacokinetics; Species differences

Indexed keywords

ACETYLSALICYLIC ACID; ARYLAMINE ACETYLTRANSFERASE; BENZOIC ACID; BENZYL ALCOHOL; BREAST CANCER RESISTANCE PROTEIN; CARPROFEN; GLUCURONOSYLTRANSFERASE 1A1; GLUCURONOSYLTRANSFERASE 1A2; GLUCURONOSYLTRANSFERASE 1A3; GLUCURONOSYLTRANSFERASE 1A4; GLUCURONOSYLTRANSFERASE 1A6; GLUCURONOSYLTRANSFERASE 1A9; GLYCOSYLTRANSFERASE; PARACETAMOL; PIROXICAM; PROPOFOL; SALICYL GLUCURONIDE; SALICYLIC ACID DERIVATIVE; SALICYLURIC ACID; THIOPURINE METHYLTRANSFERASE; UNCLASSIFIED DRUG;

ABCG2 DEFICIENCY; ANOREXIA; CAT; CHRONIC DRUG ADMINISTRATION; CHRONIC PAIN; DIARRHEA; DOG; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG CONTRAINDICATION; DRUG DISPOSITION; DRUG DISTRIBUTION; DRUG EFFECT; DRUG EFFICACY; DRUG ELIMINATION; DRUG GLUCURONIDATION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG METABOLISM; DRUG SAFETY; DRUG SENSITIVITY; DRUG TOLERABILITY; ENZYME DEFICIENCY; FEVER; GASTROINTESTINAL IRRITATION; GLUCURONIDATION DEFICIENCY; HEINZ BODY; HUMAN; INFLAMMATION; MALAISE; MOLECULAR DYNAMICS; N ACETYLTRANSFERASE 2 DEFICIENCY; NONHUMAN; NUCLEOTIDE SEQUENCE; PAIN; PROPOFOL INFUSION SYNDROME; REPEATED DRUG DOSE; REVIEW; RNA SEQUENCE; SENSITIVITY ANALYSIS; SEQUENCE ANALYSIS; SINGLE DRUG DOSE; SPECIES DIFFERENCE; THIOPURINE METHYLTRANSFERASE DEFICIENCY; ULCER;

EID: 84880928583     PISSN: 01955616     EISSN: 18781306     Source Type: Journal    
DOI: 10.1016/j.cvsm.2013.05.002     Document Type: Review

References (72)

1. Obach R.S., Lombardo F., Waters N.J. Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Drug Metab Dispos 2008, 36(7):1385-1405.
2. Parton K., Balmer T.V., Boyle J., et al. The pharmacokinetics and effects of intravenously administered carprofen and salicylate on gastrointestinal mucosa and selected biochemical measurements in healthy cats. JVet Pharmacol Ther 2000, 23(2):73-79.
3. Waters D.J., Bowers L.D., Cipolle R.J., et al. Plasma salicylate concentrations in immature dogs following aspirin administration: comparison with adult dogs. JVet Pharmacol Ther 1993, 16(3):275-282.
4. Greenblatt D.J., Abernethy D.R., Boxenbaum H.G., et al. Influence of age, gender, and obesity on salicylate kinetics following single doses of aspirin. Arthritis Rheum 1986, 29(8):971-980.
5. Savides M.C., Oehme F.W., Nash S.L., et al. The toxicity and biotransformation of single doses of acetaminophen in dogs and cats. Toxicol Appl Pharmacol 1984, 74(1):26-34.
6. Volak L.P., Hanley M.J., Masse G., et al. Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2013, 75(2):450-462.
7. Cleale R.M., Muir W.W., Waselau A.C., et al. Pharmacokinetic and pharmacodynamic evaluation of propofol administered to cats in a novel, aqueous, nano-droplet formulation or as an oil-in-water macroemulsion. JVet Pharmacol Ther 2009, 32(5):436-445.
8. Lee S.H., Ghim J.L., Song M.H., et al. Pharmacokinetics and pharmacodynamics of a new reformulated microemulsion and the long-chain triglyceride emulsion of propofol in beagle dogs. Br J Pharmacol 2009, 158(8):1982-1995.
9. Taylor P.M., Delatour P., Landoni F.M., et al. Pharmacodynamics and enantioselective pharmacokinetics of carprofen in the cat. Res Vet Sci 1996, 60(2):144-151.
10. Schmitt M., Guentert T.W. Biopharmaceutical evaluation of carprofen following single intravenous, oral, and rectal doses in dogs. Biopharm Drug Dispos 1990, 11(7):585-594.
11. Holazo A.A., Chen S.S., McMahon F.G., et al. The influence of liver dysfunction on the pharmacokinetics of carprofen. JClin Pharmacol 1985, 25(2):109-114.
12. Iwakawa S., Suganuma T., Lee S.F., et al. Direct determination of diastereomeric carprofen glucuronides in human plasma and urine and preliminary measurements of stereoselective metabolic and renal elimination after oral administration of carprofen in man. Drug Metab Dispos 1989, 17(4):414-419.
13. Heeb H.L., Chun R., Koch D.E., et al. Single dose pharmacokinetics of piroxicam in cats. JVet Pharmacol Ther 2003, 26(4):259-263.
14. Galbraith E.A., McKellar Q.A. Pharmacokinetics and pharmacodynamics of piroxicam in dogs. Vet Rec 1991, 128(24):561-565.
15. Guentert T.W., Defoin R., Mosberg H. The influence of cholestyramine on the elimination of tenoxicam and piroxicam. Eur J Clin Pharmacol 1988, 34(3):283-289.
16. Merck veterinary manual. Available at: Accessed January 25, 2013. http://www.merckvetmanual.com/mvm/index.jsp%3fcfile%3dhtm/bc/214009.htm.
17. Chen Y., Kuehl G.E., Bigler J., et al. UGT1A6 polymorphism and salicylic acid glucuronidation following aspirin. Pharmacogenet Genomics 2007, 17(8):571-579.
18. Davis L.E., Westfall B.A. Species differences in biotransformation and excretion of salicylate. Am J Vet Res 1972, 33(6):1253-1262.
19. Schachter D., Kass D.J., Lannon T.J. The biosynthesis of salicyl glucuronides by tissue slices of various organs. JBiol Chem 1959, 234(1):201-205.
20. Forman W.B., Davidson E.D., Webster L.T. Enzymatic conversion of salicylate to salicylurate. Mol Pharmacol 1971, 7(3):247-259.
21. Vessey D.A., Lau E., Kelley M., et al. Isolation, sequencing, and expression of a cDNA for the HXM-A form of xenobiotic/medium-chain fatty acid:CoA ligase from human liver mitochondria. JBiochem Mol Toxicol 2003, 17(1):1-6.
22. Kelley M., Vessey D.A. Isolation and characterization of mitochondrial acyl-CoA: glycine N-acyltransferases from kidney. JBiochem Toxicol 1993, 8(2):63-69.
23. Irizarry K.J., Malladi S.B., Gao X., et al. Sequencing and comparative genomic analysis of 1227 Felis catus cDNA sequences enriched for developmental, clinical and nutritional phenotypes. BMC Genomics 2012, 13:31.
24. Nash S.L., Savides M.C., Oehme F.W., et al. The effect of acetaminophen on methemoglobin and blood glutathione parameters in the cat. Toxicology 1984, 31(3-4):329-334.
25. Larson A.M., Polson J., Fontana R.J., et al. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology 2005, 42(6):1364.
26. James L.P., Mayeux P.R., Hinson J.A. Acetaminophen-induced hepatotoxicity. Drug Metab Dispos 2003, 31(12):1499.
27. McConkey S.E., Grant D.M., Cribb A.E. The role of para-aminophenol in acetaminophen-induced methemoglobinemia in dogs and cats. JVet Pharmacol Ther 2009, 32(6):585-595.
28. Court M.H., Greenblatt D.J. 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(4):355.
29. Court M.H., Greenblatt D.J. Molecular basis for deficient acetaminophen glucuronidation in cats. An interspecies comparison of enzyme kinetics in liver microsomes. Biochem Pharmacol 1997, 53(7):1041.
30. Gelotte C.K., Auiler J.F., Lynch J.M., et al. Disposition of acetaminophen at 4, 6, and 8 g/day for 3 days in healthy young adults. Clin Pharmacol Ther 2007, 81(6):840-848.
31. Prescott L.F. Kinetics and metabolism of paracetamol and phenacetin. Br J Clin Pharmacol 1980, 10(Suppl 2):291S-298S.
32. Taylor P.M., Chengelis C.P., Miller W.R., et al. Evaluation of propofol containing 2% benzyl alcohol preservative in cats. JFeline Med Surg 2012, 14(8):516-526.
33. Pascoe P.J., Ilkiw J.E., Frischmeyer K.J. The effect of the duration of propofol administration on recovery from anesthesia in cats. Vet Anaesth Analg 2006, 33(1):2-7.
34. Andress J.L., Day T.K., Day D. The effects of consecutive day propofol anesthesia on feline red blood cells. Vet Surg 1995, 24(3):277-282.
35. Roberts R.J., Barletta J.F., Fong J.J., et al. Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study. Crit Care 2009, 13(5):R169.
36. Diedrich D.A., Brown D.R. Analytic reviews: propofol infusion syndrome in the ICU. JIntensive Care Med 2011, 26(2):59-72.
37. Simons P.J., Cockshott I.D., Douglas E.J., et al. Species differences in blood profiles, metabolism and excretion of 14C-propofol after intravenous dosing to rat, dog and rabbit. Xenobiotica 1991, 21(10):1243-1256.
38. Favetta P., Degoute C.S., Perdrix J.P., et al. Propofol metabolites in man following propofol induction and maintenance. Br J Anaesth 2002, 88(5):653-658.
39. Court M.H., Duan S.X., Hesse L.M., et al. Cytochrome P-450 2B6 is responsible for interindividual variability of propofol hydroxylation by human liver microsomes. Anesthesiology 2001, 94(1):110.
40. Hay Kraus B.L., Greenblatt D.J., Venkatakrishnan K., et al. Evidence for propofol hydroxylation by cytochrome P4502B11 in canine liver microsomes: breed and gender differences. Xenobiotica 2000, 30(6):575.
41. Stratford N., Murphy P. Effect of lipid and propofol on oxidation of haemoglobin by reactive oxygen species. Br J Anaesth 1997, 78(3):320-322.
42. Lascelles B.D., Court M.H., Hardie E.M., et al. Nonsteroidal anti-inflammatory drugs in cats: a review. Vet Anaesth Analg 2007, 34(4):228.
43. Sparkes A.H., Heiene R., Lascelles B.D., et al. ISFM and AAFP consensus guidelines: long-term use of NSAIDs in cats. JFeline Med Surg 2010, 12(7):521-538.
44. Ray J.E., Wade D.N. The pharmacokinetics and metabolism of 14C-carprofen in man. Biopharm Drug Dispos 1982, 3(1):29-38.
45. Magdalou J., Chajes V., Lafaurie C., et al. Glucuronidation of 2-arylpropionic acids pirprofen, flurbiprofen, and ibuprofen by liver microsomes. Drug Metab Dispos 1990, 18(5):692-697.
46. Tracy T.S., Hutzler J.M., Haining R.L., et al. Polymorphic variants (CYP2C9*3 and CYP2C9*5) and the F114L active site mutation of CYP2C9: effect on atypical kinetic metabolism profiles. Drug Metab Dispos 2002, 30(4):385-390.
47. Richardson C.J., Blocka K.L., Ross S.G., et al. Piroxicam and 5'-hydroxypiroxicam kinetics following multiple dose administration of piroxicam. Eur J Clin Pharmacol 1987, 32(1):89-91.
48. Hobbs D.C., Twomey T.M. Piroxicam pharmacokinetics in man: aspirin and antacid interaction studies. JClin Pharmacol 1979, 19(5-6):270-281.
49. Richardson C.J., Blocka K.L., Ross S.G., et al. Effects of age and sex on piroxicam disposition. Clin Pharmacol Ther 1985, 37(1):13-18.
50. Court M.H., Zhang X., Ding X., et al. Quantitative distribution of mRNAs encoding the 19 human UDP-glucuronosyltransferase enzymes in 26 adult and 3 fetal tissues. Xenobiotica 2012, 42(3):266.
51. Hartiala K.J. Studies on detoxication mechanisms. III. Glucuronide synthesis of various organs with special reference to the detoxifying capacity of the mucous membrane of the alimentary canal. Ann Med Exp Biol Fenn 1955, 33(3):239-245.
52. Gregus Z., Watkins J.B., Thompson T.N., et al. Hepatic phase I and phase II biotransformations in quail and trout: comparison to other species commonly used in toxicity testing. Toxicol Appl Pharmacol 1983, 67(3):430-441.
53. Watkins J.B., Klaassen C.D. Xenobiotic biotransformation in livestock: comparison to other species commonly used in toxicity testing. JAnim Sci 1986, 63(3):933-942.
54. French M.R., Bababunmi E.A., Golding R.R., et al. The conjugation of phenol, benzoic acid, 1-naphthylacetic acid and sulphadimethoxine in the lion, civet and genet. FEBS Lett 1974, 46(1):134-137.
55. Capel I.D., French M.R., Millburn P., et al. The fate of (14C)phenol in various species. Xenobiotica 1972, 2(1):25-34.
56. Shrestha B., Reed J.M., Starks P.T., 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(3):e18046.
57. Yeh S.Y., Chernov H.I., Woods L.A. Metabolism of morphine by cats. JPharm Sci 1971, 60(3):469-471.
58. Schillings R.T., Sisenwine S.F., Schwartz M.H., et al. Lorazepam: glucuronide formation in the cat. Drug Metab Dispos 1975, 3(2):85-88.
59. Emudianughe T.S., Caldwell J., Sinclair K.A., et al. Species differences in the metabolic conjugation of clofibric acid and clofibrate in laboratory animals and man. Drug Metab Dispos 1983, 11(2):97-102.
60. Matsumoto S., Takahashi M., Kitadai N., et al. Astudy of metabolites isolated from the urine samples of cats and dogs administered orbifloxacin. JVet Med Sci 1998, 60(11):1259-1261.
61. Zoran D.L., Boeckh A., Boothe D.M. Hyperactivity and alopecia associated with ingestion of valproic acid in a cat. JAm Vet Med Assoc 2001, 218(10):1587-1589. 1580.
62. Ebner T., Schanzle G., Weber W., et al. Invitro glucuronidation of the angiotensin II receptor antagonist telmisartan in the cat: a comparison with other species. JVet Pharmacol Ther 2013, 36(2):154-160.
63. Bridges J.W., French M.R., Smith R.L., et al. The fate of benzoic acid in various species. Biochem J 1970, 118(1):47-51.
64. Janz R. Benzoic acid hazard in cat preparations. Vet Rec 1989, 124(22):595.
65. Bedford P.G., Clarke E.G. Experimental benzoic acid poisoning in the cat. Vet Rec 1972, 90(3):53-58.
66. Trepanier L.A., Cribb A.E., Spielberg S.P., et al. Deficiency of cytosolic arylamine N-acetylation in the domestic cat and wild felids caused by the presence of a single NAT1-like gene. Pharmacogenetics 1998, 8(2):169-179.
67. Trepanier L.A., Ray K., Winand N.J., 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(1):73-80.
68. Beale K.M., Altman D., Clemmons R.R., et al. Systemic toxicosis associated with azathioprine administration in domestic cats. Am J Vet Res 1992, 53(7):1236-1240.
69. Salavaggione O.E., Yang C., Kidd L.B., et al. Cat red blood cell thiopurine S-methyltransferase: companion animal pharmacogenetics. JPharmacol Exp Ther 2004, 308(2):617-626.
70. White S.D., Rosychuk R.A., Outerbridge C.A., et al. Thiopurine methyltransferase in red blood cells of dogs, cats, and horses. JVet Intern Med 2000, 14(5):499-502.
71. Foster A.P., Shaw S.E., Duley J.A., et al. Demonstration of thiopurine methyltransferase activity in the erythrocytes of cats. JVet Intern Med 2000, 14(5):552-554.
72. Ramirez C.J., Minch J.D., Gay J.M., et al. Molecular genetic basis for fluoroquinolone-induced retinal degeneration in cats. Pharmacogenet Genomics 2011, 21(2):66-75.