Clenbuterol and other b-agonists, are they an option for meat production or a threat for public health?

Héctor Sumano L; Luis Ocampo C; Lilia Gutiérrez O

2002, Number 2

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Vet Mex 2002; 33 (2)

Clenbuterol and other b-agonists, are they an option for meat production or a threat for public health?

Sumano LH, Ocampo CL, Gutiérrez OL

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Language: English/Spanish
References: 119
Page: 137-159
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ABSTRACT

The correct assessment of each so-called Β-adrenergic agonist, motivated the authors to carry out this review of the scientific literature. In Mexico, as in many countries worldwide, some Β-adrenergic agonists are used to improve carcass performance in various domestic species. From this group, chemically classified as phenethanolamine derivatives, clenbuterol, ractopamine and zilpaterol, stand out. In this review, chemical and pharmacological differences among these latter agents are emphasized; in particular those aspects that concern public health. Derived from references and information compiled, it becomes evident that clenbuterol is capable of enhancing carcass performance in cattle and other species. However its use may jeopardize, to some extent, public health. But above all, at present, the use of clenbuterol to improve performance in food producing animals must be viewed as an illegal act; hence, liable to legal punishment. It is only fair to state that clenbuterol is neither carcinogenic, nor mutagenic, and only embryotoxic at very high doses. This drug is dangerous to human beings in terms of the cardiovascular stimulatory effects that may derive from the consumption of meat products from animals in which a 4-week withdrawal period was not observed. At present, no fatalities have been related to this drug. In contrast, ractopamine and zilpaterol produce extremely weak pharmacological actions in man, and are so rapidly metabolized and cleared from the animal's body, that it is virtually impossible to regard them as potential causes of drug poisoning in human beings, even after consuming meat products derived from animals medicated with these drugs and were no withdrawal time was enforced.

REFERENCES

1. Scott JS, Berney CE, Derksen FJ, Robinson NE. Beta-adrenergic receptor activity in ponies with recurrent obstructive pulmonary disease. Am J Vet Res 1991;52:1416-1422.
2. Sillence MN, Mathews ML, Badran TW, Pegg GG. Effects of clenbuterol on growth in underfed cattle. Austr J Agric Res 2000;51:401-406.
3. Peters AR. b-agonists as repartitioning agents: a review. Vet Rec 1989;124:417-420.
4. Sumano LH. Quinolonas y fluoroquinolonas en medicina veterinaria. Vet Méx 1993;2:24-28.
5. Ocampo CL, Sumano LH, Paez ED. Farmacocinética y eficacia clínica del tianfenicol en pollo de engorda. Vet Méx 2000;31:89-93.
6. Sumano LH, Ocampo CL. Farmacología veterinaria. 2a ed. México (DF): McGraw Hill/Interamericana, 1997.
7. Martin LE, Hobson JC, Page JA, Harrisson AC. Metabolic studies of Salbutamol-3H: a new bronchodilator in rat, rabbit, dog, and man. Eur J Pharmacol 1971;14: 183-199.
8. Morgan DJ. Clinical pharmacokinetics of beta-agonists. Clin Pharmacocinet 1990;18:270-294.
9. Murphy PJ, Williams TL, Kau DLK. Disposition of dobutamine in the dog. G Pharmacol Exp Ther 1976;199:423-431.
10. Wallis CJ. Salbutamol, salmeterol-a chemist´s perpective. Chim Ther 1993;20:265-291.
11. Nazzal CA. The clinical pharmacology of clenbuterol. South-West Vet 1985;36:121-125.
12. Witkamp RF, Van Miert A. Pharmacology and therapeutic use of b2 – agonists. Thessaloniki 1992;8:75-88.
13. Witkamp RF. Pharmacological and toxicological properties of b-adrenergic agonists. In: Enne G, Kuiper HA, Valentini A, editors. Residues of veterinary drugs and mycotoxine in animal products: new methods for risk assessment and quality control. Memorias de la conferencia vía Internet (Listserver Meatqual); 1994, 15 abril - 31 agosto; Wageningen Pers, Wageningen, Netherlands, 1996:113-123.
14. Moffat AC, Jackson JV, Moss MS, Widdop B. Clarkess isolation and identification of drugs. 2nd ed. London (UK): The Pharmaceutical Press, 1986.
15. Tariq M, Al-Badr AA. Isoprotrenol. Profiles Drug Subst 1985;14:391-422.
16. Turberg MP, Macy TD, Lewis JJ, Coleman MR. Determination of raptopamine hydrochloride in swine and turkey tissues by liquid chromatography with colourmetric detection. J Am Org Anal Chem 1995;78:1394-1402.
17. Lund W. The pharmaceutical codex. 12th ed. London (UK): The Pharmaceutical Press, 1994.
18. Ahuja S, Ashman J. Terbutaline sulfate. Profiles Drug Subst 1990;19:601-625.
19. Carlström D, Bergin R, Falkenberg G. Molecular characteristics of biogenic monoamines and their analogs. Q Rev Biophys 1973;6:257-310.
20. Hieble JP, Bondinell WE, Ruffolo RR. a and b-adrenoceptors: from the gene to the clinic. 1. Molecular biology and adrenoceptor subclassification. J Med Chem 1995;38:3415-3444.
21. Reynolds EF, Parfitt K, Parsons AV, Sweetman S, Martindale C. The extra pharmacopoeia. London (UK): The Pharmaceutical Press, 1989.
22. Courtheyn D, Moermans R, Schilt R, Boenke A. Beta-agonists in animal feed. II. Optimization of the extraction. Food Additives Contam 1996;13:493-509.
23. Wilson RT, Groneck JM, Holland KP, Henry AC. Determination of clenbuterol in cattle, sheep, and swine tissues by electron ionization gas chromatography/mass spectrometry. J Am Org Anal Chem 1994;77: 917-924.
24. Ruffolo RE. Chirality in a and b-adrenoceptor agonists and antagonists. Tetrahedron 1991;47:9953-9980.
25. Martín R, Hernández PE, Sanz B. Revisión: residuos de tratamientos veterinarios y salud pública. Rev Esp Cienc Aliment 1992;32:5.
26. Waldeck B, Widmark E. Steric aspects of agonism and antagonism at b-adrenoceptors: experiments with the enantiomers of clenbuterol. Pharmacol Toxicol 1995;56:221-227.
27. Kaiser G, Wiemer G, Kremer G, Dietz J, Palm D. Identification and quantification of b- adrenoceptor sites in red blood cells. Naunyn-Schmiedeberg´s Arch Pharmacol 1978;305:41-51.
28. Mersmann HJ, McNeel RL. Ligand binding to the porcine adipose tissue beta-adrenergic receptor. J Anim Sci 1992;70:787-797.
29. Mazzoni L, Naef R, Chapman ID, Morley J. Hyperresponsiveness of the airways following exposure of Guinea- pigs to rasemic mixtures and distomers of b-selective sympatomimetics. Pulm Pharmacol 1994;7:367-376.
30. Thompsom MJ, Huss P, Unverferth DV, Fasola A, Leier CV. Hemodynamic effects of intravenous butopamine in congestive heart failure. Clin Pharmacol Ther 1980;28:324-334.
31. Yen TT, Anderson DB, Veehuizen EL. Phenethanolamines: reduction of fat and increase of muscle from mice to pigs. In: Lardy H, Stratman, editor. Hormones, thermogenesis, and obesity. New York: Elsevier, 1989:455-464.
32. Ricke EA, Larson GL, Smith DJ, Feil VJ, Caton JS. Influence of intraperitoneal administration of ractopamine HCl stereoisomers on growth, protein retention, and carcass compotition in rats fed commercial diets. J Anim Sci 1996;74:210.
33. Jeppson AB, Johansson U, Wldeck B. Steric aspect of agonism and antagonism at beta-adrenoceptors: experiments with the enantiomers of terbutaline and pindolol. Pharmacol Toxicol 1984;54:285-291.
34. Shaw WN, Schmiegel KK, Yen TT, Toomey RE, Meyers DB, Mills J. LY7977A novel compound for weight control. Life Sci 1981;29:2091-2101.
35. Yen TT, McKee MM, Stamm NB, Bemis KG. Stimulation of cyclic AMP and lipolysis in adipose tissue of normal and obese Auy / a mice by LY/), a phenethanolamine and stereoisomers. Life Sci 1983;32:1515-1522.
36. Johnson M. Salmeterol. Med Res Rev 1995;15:225-257.
37. Herbert F, Hovell FD, Reeds PJ. Beta-agonists and their effects on animal growth. Nutr Soc 1985; 44:5.
38. Jones RW, Easter RA, McKeith FK, Dalrymple RH, Maddock HM, Bechtel PJ. Beta-agonists. J Anim Sci 1985;61:905.
39. Kuiper HA, Noordam MY, Dooren-Flipsen MMH, Van Schilt R., Roos AH. Illegal use of beta-adrenergic agonists. J Anim Sci 1998;76:195-202.
40. Slocombe RF, Covelli G, Baylay WM. Respiratory mechanics of horses during stepwise treadmill exercise tests, and the effect of clenbuterol pretreatment on them. Austr Vet J 1992;69:221-225.
41. Dodam JR, Moor RE, Olson NC, Exposito AJ, Fawcett TA, Huang YC, et al. Effects of clenbuterol hydrochloride on pulmonary gas exchange and hemodynamics in anesthetized horses. Am J Vet Res 1993;54:776-782.
42. Reinhold P. Oscillatory measurements, blood gas analysis and clinical observations after intravenous clenbuterol administration in healthy and acutely pneumonic calves. Vet Res 1993;17:143-151.
43. Meinen K, Rominger KL, Hermer M, Rahn M, Kanitz T. Oral tocolytic therapy with clenbuterol-determination of the plasma level. Ztschr Geburtshilfe Perinatol 1988;192:158-162.
44. Yeagley C, Caritis SN, Ruzycky AL. Contraction inhibition by beta-agonists progressively decreases before labor in the rat myometrium. Am J Obstetr Gynecol 1996;174:1637-42.
45. Gastal MO, Gastal EL, Torres CAA, Ginther OJ. Effect of oxytocin, prostaglandin F2 alpha, and clenbuterol on uterine dynamics in mares. Theriogenology 1998;50:521-553.
46. Meredith S, Kiesling DO. The effect of flumethasone, clenbuterol and oxytocin on time of lambing in crossbred ewes. J Dairy Sci 1989;72:383-384.
47. Gastal MO, Gastal EL, Torres CAA, Ginther OJ. Effect of oxytocin, prostaglandin F2 alpha, and clenbuterol on uterine dynamics in mares Theriogenology 1998;50:521-534.
48. Plant JW, Bowler JK. Controlled parturition in sheep using clenbuterol hydrochloride. Aust Vet J 1988:65:91-93.
49. Mitchell GA, Glora D. Illegal use of (b-adrenergic agonists in the United States. J Anim Sci 1998; 76:208-211.
50. Elliot CT, McCaughey WJ, Crooks SR, McEvoy JD, Kennedy DG. Residues of clenbuterol in cattle receiving therapeutic doses: implications for differentiating between legal and illegal use. Vet Q 1995;17:100-102.
51. De Wasch K, De Brabander H, Courtheyn D. LC-MS-MS to detect and identify four beta-agonists and quantify clenbuterol in liver. Analyst 1998;123:2701-2705.
52. Hooijerink H, Schilt R, Van Bennekom EO, Huf FA. Determination of beta-sympathomimetics in liver and urine by immunoaffinity chromatography and gas chromatography-mass-selective detection. J Chrom B 1994;660:303-313.
53. Cerni L, Biancotto G, Tondolo A, Bogoni P. Dexamethasone and clenbuterol detection by enzyme immunoassay in bovine liver tissue: a new multiresidue extraction procedure. Food Agr Immun 1998;10:307-315.
54. Boenisch B, Quirke JF. Safety assessment of b-agonists. In: Kuiper HA, Hoogenboom LAP, editors. In vitro toxicological studies and real time analysis of residues in food. Wageningen, The Netherlands: RIKILT–DLO-Wageningen, 1992:102-124.
55. Smith DJ. The pharmacokinetics, metabolism, and tissue residues of beta-adrenergic agonists in livestock. J Anim Sci 1998;76:173-194.
56. Dalidowicz JE, Thomson TD, Babbitt GE, Hutson DH. Ractopamine hydrochloride, a phenethanolamine repartitioning agent: metabolism and tissue residues. Xenobiotics Food Producing Ann 1992;503:234-243.
57. Smith DJ, Feil VJ, Huwe JK, Paulson GD. Metabolism and disposition of ractopamine hydrochloride by turkey poults. Drug Metabol Disposit 1993;21:624-633.
58. Polettini A, Montagna M, Hogendoorn EA, Dijkman E, Van Zoonen P, Van Ginkel LA. Applicability of coupled-column liquid chromatography to the analysis of beta-agonists in urine by direct sample injection I. Development of a single-residue reversed-phase liquid chromatography-UV method for clenbuterol and selection of chromatographic conditions suitable for multi-residue analysis. J Chroma 1995;695:19-31.
59. Anonymous. Evaluation of certain veterinary drug residues in food. World Health Organization Technical Report Series 1993;Issue 832:1-62.
60. Mersmann HJ. Overview of the effects of b-adrenergic receptor agonist on animal growth including mechanims of action. J Anim Sci 1998;76:160-172.
61. Ricks CA, Baker PK, Dalrymple RH. Use of repartitioning agents to improve performance and body composition of meat animals. Reciprocal Meat 1984;37:5-11.
62. Ornelas GJJ. Evaluación del isoproterenol sobre el comportamiento productivo y calidad de la canal de cerdos en finalización (tesis de maestría) México (DF): Facultad de Medicina Veterinaria y Zootecnia. UNAM, 1992.
63. Vanbelle M, Teller E. The use of beta-agonists for meat production: considerations, results and reflections [clenbuterol, cimaterol, salbutamol, ractopamine]. Louvain-la-Neuve 1991;56:37.
64. Mejía GCA, Menéndez TM, Cuaron IJA. Ractopamine en dieta para cerdas: desarrollo y crecimiento. Vet Méx 1995;26:374-376.
65. Moody DE, Hanock DL, Anderson DB. Phenethanolamine repartitioning agents. Research and development. Indianapolis, IN: Elanco Animal Health, 1999.
66. Penny RH, Guise HJ, Rolph TP, Tait JA, Johnston AM, Kempson SA, Gettinby G. Influence of the beta-agonist salbutamol on claw horn lesions and walking soundness in finishing pigs. Vet Rec 1994;35:374-381.
67. Hansen JA, Yen JT, Klindt J, Nelssen JL, Goodband RD. Effects of somatotropin and salbutamol in three genotypes of finishing barrows: blood hormones and metabolites and muscle characteristics. J Anim Sci 1997;75:1810-1821.
68. Hanrahan LP. Beta agonists and their effects on animal growth and carcass quality. Am Chem Soc 1992;503: 234-243.
69. Rehfeldt C, Schadereit R, Weikard R, Reichel K. Effect of clenbuterol on growth, carcass and skeletal muscle characteristics in broiler chickens. Br Poultry Sci 1997;38:366-373.
70. Buhr BL, Hayenga ML. Evaluation of the economic impacts of growth promotors in the U.S. livestock and meat sector. Rev Agric Econ 1994;16:159-173.
71. Ocampo L, Cortez U, Sumano H, Avila E. Use of low doses of clenbuterol to reduce incidence of ascites syndrome in broilers. Poultry Sci 1998;77:1297-1299.
72. Cortes PU, Avila GE, Ocampo CL, Sanchez RS, Cortes CC. The effect of clenbuterol on broiler growth and prevention of ascites syndrome. Reunión Nacional de Investigación Pecuaria; 1996 2-4 diciembre; Cuernavaca (Morelos) México. Cuautitlán, Edo. de México, Facultad de Medicina Veterinaria y Zootecnia, Facultad de Estudios Superiores, Cuautitlán/Universidad Nacional Autónoma de México, Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias, 1996:56-64.
73. Yang YT, McElligott MA. Multiple actions of b-adrenergic agonists on skeletal muscle and adipose tissue. Biochemistry 1989;261:1-10.
74. Smith SB, Gracia DK, Anderson DB. Elevation of a specific mRNA in longissimus muscle of steers fed ractopamine. J Anim Sci 1989;67:3495-3520.
75. Helferich WG, Jump DB, Anderson DB, Skjaerlund DM, Merkel RA, Bergen WG. Skeletal muscle a-actin synthesis is increased pretranslational in pig fed the phenetholamine ractopamine. Endocrinology 1990;126:3096-3100.
76. Higgins JA, Lasslett YV, Bardsley RG, Buttery PJ. The relation between dietary restriction or clenbuterol treatment on muscle growth and calpain proteinase (EC 3.4.22.17) and calpastain activities in lambs. Br J Nutr 1988;60:645-652.
77. Adeola O, McBride BW, Young LG. Metabolic responses induced by isoproterenol in ractopamine-fed pigs. J Nutr 1992;122:1280-1286.
78. Preitner F, Muzzin P, Revelli JP, Seydoux J, Galitzky J, Berlan M, et al. Metabolic response to various beta-adrenoceptor agonists in beta 3-adrenoceptor knockout mice: evidence for a new beta-adrenergic receptor in brown adipose tissue. Br J Pharm 1998;124:1684-1688.
79. MacNeel RL, Mersmann HJ. b-adrenergic receptor subtype transcripts in porcine adipose tissue. J Anim Sci 1995;73:1962-1971.
80. Mersmann HJ. Acute metabolic effects of adrenergic agents in swine. Am J Physiol 1987;252:85-95.
81. Mersmann HJ. Evidence of classic b3-adrenergic receptors in porcine adipocytes. J Anim Sci 1996;74:984-992.
82. Mersmann HJ. Acute changes in blood flow in pigs infused with b-adrenergic agonists. J Anim Sci 1989a;67:2913-2920.
83. Mersmann HJ. Influence of infused b-adrenergic agonists on porcine blood metabolites and catecholamines. J Anim Sci 1989b;67:2633-2645.
84. Mersmann HJ. Species variation in mechanisms for modulation of growth by beta-adrenergic receptors. J Nutr 1995;125:1777-1782.
85. Sauer MJ, Dave M, Lake BG, Manchee GR, Howells LC, Coldham NG. Beta2-agonist abuse in food producing animals: use of in vitro liver preparations to assess biotransformation and potential target residues for surveillance. Xenobiotic 1999;29:483-497.
86. Moloney A, Allen P, Joseph R, Tarrant V. Influence of beta-adrenergic agonists and similar compounds on growth. New York: Elsevier Science Publishing, 1991:455-513.
87. Sauer MJ, Anderson SPL. In vitro and in vivo studies of drug residue accumulation in pigmented tissues. Analyst 1994;119:2553-2556.
88. Sauer MJ, Pickett RJH, Limer S, Dixon SN. Distribution and elimination of clenbuterol in tissues and fluids following prolonged oral administration at a growth promoting dose. J Vet Pharmacol Ther 1995;18:81-86.
89. Howells L, Godfrey M, Sauer MS. Melanine as an absorbent for drug residues. Analyst 1994;119:2691-2693.
90. Elliott CT, Thompson CS, Arts CJM, Crooks SRH, Baak MJ, Van Verheij ER, et al. Screening and confirmatory determination of ractopamine residues in calves treated with growth promoting doses of the beta-agonist. Analyst 1998;123:1103-1107.
91. FAO/WHO Expert Committee on Food Additives. Evaluation of certain veterinary drug residues in food. Fortieth report of the Joint World Health Organization. WHO-Technical-Report-Series. New York: WHO, 1993:832-862.
92. FAO/WHO Expert Committee on Food Additives. Residues of some veterinary drugs in animals and foods. Monographs prepared by the Fourth Meeting of the Joint FAO/WHO Expert Committee on Food Additives; 1992; June 8-18; Geneva, Switzerland. Geneva, Switzerlands Food and Agriculture Organization, 1992;614-621.
93. Martinez-Navarro JF. Food poisoning related to the consumption of illicit beta-agonist in livers. Lancet 1990;336:1311.
94. Pulse C, Lamison D, Keck G, Bosvironnais C, Nicolas J, Descotes J. Collective human poisonings by clenbuterol residues in veal liver. Vet Hum Toxicol 1991;33:480-481
95. Prather ID, Brown DE, North P, Wilson JR. Clenbuterol: a substitute for anabolic steroids? Med Sci Sports Exerc 1994;27:1118-1121.
96. Von Ahnen S. Analytische Untersuchungen über Nährstoffumverteilende Wachstumspromotoren beim Rind (Ph. D. dissertation). München, Germany: Universität München, 1994.
97. Meyer HHD. The illegal practice and resulting risks vs the controlled use of licensed drugs: views in the present situation in Germany. Ann Rech Vet 1991;22:299-304.
98. Stoffel B, Meyer HHD. Effects of the b-adrenergic agonist clenbuterol in cows: lipid metabolism, milk production, pharmacokinetics, and residues. J Anim Sci 1993;71:1875-1881.
99. Smith DJ, Paulson GD. Identification and stereochemical composition of ractopamine (RAC) glucuronides excreted in turkey bile. J Anim Sci 1993;71:202.
100. Dalidowicz JE, Thomson TD, Babbitt GE. Ractopamine hydrochoride, a phenethanolamine repartitioning agent: metabolism and residues. In: Hutson DH, Hawkins DR, Paulson GD, Struble CB, editors. Xenobiotics and food-producing animals. Washington (DC): American Chemical Society, 1992:234-243.
101. Smith DJ, Giddings JM, Feil VJ, Paulson GD. Identification of ractopamine hydrochloride metabolites excreted into rat bile. Xenobiotica 1995;25:511-520.
102. Smith DJ, Paulson GD. Growth characteristics of rats receiving ractopamine hydrochloride and the metabolic disposition of ractopamine hydrochloride after oral or intraperitoneal administration. J Anim Sci 1994;72:404-414.
103. Smith DJ, Paulson GD. Distribution, elimination, and residues of [C] clenbuterol HCl in Holstein calves. J Anim Sci 1997;75:454-461.
104. Pou K, Adam A, Lamothe P, Gravel P, Messier J, Gravel A, Ong H. Serum and urinary levels of salbutamol after chronic oral administration in a calf. Can Vet J 1992;33:467-468.
105. Malucelli A, Ellendorff F, Meyer HHD. Tissue distribution and residues of clenbuterol, salbutamol and terbutharine in tissues of treated broiler chickens. J Anim Sci 1994;72:1555-1560.
106. Gleixner A. Probenecid markedly reduces urinary excretion of ethinylestradiol and trimethoprim slightly reduces urinary excretion of clenbuterol. Food Addit Contamin 1998;15:415-420.
107. Elliot CT, McEvoy JD, Shortt HD, Crooks SRH. Effective laboratory monitoring and the abuse of the beta agonist clenbuterol in cattle. Analyst 1993;118:447-448.
108. Sumano LH, Ocampo CL. Bases farmacológicas de la vigilancia de residuos de fármacos en veterinaria. Vet Méx 1995;26:175-182.
109. Sumano LH, Brumbaugh GW. Farmacología clínica de los aminoglicósidos y los aminociclitoles en medicina veterinaria. Vet Méx 1995;26:1-15.
110. Meyer HHD, Rinke LM. The pharmacokinetics and residues of clenbuterol in veal calves. J Anim Sci 1991;69:4538-4544.
111. Hooijerink H, Schilt R, Haasnootnd W, Courtheijn D. Determination of clenbuterol in urine of calves by high performance liquid chromatography with in series ultraviolet and electrochemical detection. J Pharm Biomed A 1991;9:485-492.
112. Moloney A. Beta agonists. Feedstuffs 1983;11:13.
113. Moody DE, Hancock DL, Anderson DB. Phenethanolamine repartitioning agents. Farm animal metabolism and nutrition. Wallingford (UK): CAB Publishing, 2000:65-96.
114. Zimmer VA. Ein Malapplikation, Mehrfachapplikation und Metabolitenmuster von Clenbuterol beim Menschen. Arzneim Forsch 1976;12:1445-1450.
115. Zimmer VA. Pharmakokinetik und Metabolitenmuster von Clenbuterol beim Kaninchen und beim Hund. Arzneim Forsch 1976;12:1442-1445.
116. Kopitar VZ, Zimmer A. Pharmakokinetik und Metabolitenmuster von Clenbuterol bei der Ratte. Arzneim Forsch 1976;26:1435-1441.
117. Kallings PC, Ingvast-Larsson S, Persson-Appelgren LE, Forster HJ, Rominger KL. Clenbuterol plasma concentrations after repeated oral administration and its effects on cardio-respiratory and blood lactate responses to exercise in healthy Standardbred horses. J Vet Pharmacol Ther 1991;14:243-249.
118. Yamamoto I, Iwata K, Nakashima M. Pharmacokinetics of plasma and urine clenbuterol in man, rat, and rabbit. J Pharmacobiol Dynamics 1995;8:335-391.
119. Byrem TM, Robinson TF, Boisclair YR, Bell AW, Schwark WS, Beermann DH. Analysis and pharmacokinetics of cimaterol in growing Holstein steers. J Anim Sci 1992;70:3812-3819.