락토파민

Other Uses -> Animal Feed Additives

Pharmaceutical

168.9 Ų [M+H]+ [CCS Type: TW]

168.35 Ų [M-H]-

New animal drugs for use in animal feeds. Ractopamine. Conditions of use: (1) Swine: ... For increased rate of weight gain, improved feed efficiency, and increased carcass leanness in finishing swine fed a complete ration containing at least 16 percent crude protein from 150 lb (68 kg) to 240 lb (109 kg) body weight. Limitations: Feed continuously as sole ration. ... For improved feed efficiency and increased carcass leanness in finishing swine fed a complete ration containing at least 16 percent crude protein from 150 lb (68 kg) to 240 lb (109 kg) body weight. Limitations: Feed continuously as sole ration ... (2) Cattle: ... cattle fed in confinement for slaughter: For increased rate of weight gain and improved feed efficiency during the last 28 to 42 days on feed. Limitations: Feed continuously as sole ration during the last 28 to 42 days on feed. Not for animals intended for breeding. ... Cattle fed in confinement for slaughter: For increased rate of weight gain, improved feed efficiency, and increased carcass leanness during the last 28 to 42 days on feed. Limitations: Feed continuously as sole ration during the last 28 to 42 days on feed. Not for animals intended for breeding. /May be used in combination with tylosin and monesin/

New animal drugs for use in animal feeds. Requirement of a medicated feed mill license. Ractopamine is included on this list.

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Ractopamine hydrochloride is included on this list. /Ractopamine hydrochloride/

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Tolerances-(1) Cattle - (i) Liver (the target tissue). The tolerance for ractopamine hydrochloride (the marker residue) is 0.09 parts per million (ppm). (ii) Muscle. The tolerance for ractopamine hydrochloride (the marker residue) is 0.03 ppm. (2) Swine - (i) Liver (the target tissue). The tolerance for ractopamine hydrochloride (the marker residue) is 0.15 ppm. (ii) Muscle. The tolerance for ractopamine hydrochloride (the marker residue) is 0.05 ppm. /Ractopamine Hydrochloride/

The objectives of this study were to measure the residues of ractopamine in livers and kidneys of cattle (n = 6), sheep (n = 6), and ducks (n = 9) after treatment with dietary ractopamine for seven (sheep, ducks) or eight (cattle) consecutive days and to measure the depletion of ractopamine from urine of cattle and sheep. ... Analysis was performed with HPLC using fluorescence detection after liquid- (hydrolyzed samples) and(or) solid-phase extraction. No residues were detected in duck tissues. Liver residues in sheep averaged 24.0 and 2.6 ppb after 0- and 3-day withdrawal periods, respectively. Sheep liver residues after a 7-day withdrawal period were less than the limit of quantification (2.5 ppb). Sheep kidney residues were 65.1 and undetectable at 0- and at 3- and 7-day, withdrawal periods, respectively. Cattle liver residues were 9.3, 2.5, and undetectable after 0-, 3-, and 7-day withdrawal periods, respectively; kidney residues were 97.5, 3.4, and undetectable at the same respective withdrawal periods.

An 8-wk study of the effects of CLA, rendered animal fats, and ractopamine, and their interactive effects on growth, fatty acid composition, and carcass quality of genetically lean pigs was conducted. Gilts (n = 228; initial BW of 59.1 kg) were assigned to a 2 x 2 x 3 factorial arrangement consisting of CLA, ractopamine, and fat treatments. The CLA treatment consisted of 1% CLA oil (CLA-60) or 1% soybean oil. Ractopamine levels were either 0 or 10 ppm. Fat treatments consisted of 0% added fat, 5% choice white grease (CWG), or 5% beef tallow (BT). The CLA and fat treatments were initiated at 59.1 kg of BW, 4 wk before the ractopamine treatments. The ractopamine treatments were imposed when the gilts reached a BW of 85.7 kg and lasted for the duration of the final 4 wk until carcass data were collected. Lipids from the belly, outer and inner layers of backfat, and LM were extracted and analyzed for fatty acid composition from 6 pigs per treatment at wk 4 and 8. Feeding CLA increased (P < 0.02) G:F during the final 4 wk. Pigs fed added fat as either CWG or BT exhibited decreased (P < 0.05) ADFI and increased (P < 0.01) G:F. Adding ractopamine to the diet increased (P < 0.01) ADG, G:F, and final BW. The predicted carcass lean percentage was increased (P < 0.05) in pigs fed CLA or ractopamine. Feeding either 5% fat or ractopamine increased (P < 0.05) carcass weight. Adding fat to the diets increased (P < 0.05) the 10th rib backfat depth but did not affect predicted percent lean. Bellies of gilts fed CLA were subjectively and objectively firmer (P < 0.01). Dietary CLA increased (P < 0.01) the concentration of saturated fatty acids and decreased (P < 0.01) the concentration of unsaturated fatty acids of the belly fat, both layers of backfat, and LM. Ractopamine decreased (P < 0.01) the i.m. fat content of the LM but had relatively little effect on the fatty acid profiles of the tissues compared with CLA. These results indicate that CLA, added fat, and ractopamine work mainly in an additive fashion to enhance pig growth and carcass quality. Furthermore, these results indicate that CLA results in more saturated fat throughout the carcass.

/HUMAN EXPOSURE STUDIES/ The dose-dependent effects of ractopamine on the human cardiovascular system were studied in a limited number of human volunteers (six persons) given ascending single oral doses equal to 67, 133, 200, 333, and 597 ug/kg bw, with an interval of 48 h between doses. Occasional mild to moderate sensations of increase in heart rate and heart pounding were reported at doses of 200, 333, and 597 ug/kg bw. Dose dependent increases in heart rate and cardiac output, and shortened electromechanical systole, as measured by echocardiography, were observed. The changes appeared within the first hour after the administration of ractopamine and values gradually returned to those before treatment. The systolic blood pressure increased in a dose dependent manner. Unlike in monkeys and dogs, ractopamine had little effect on diastolic blood pressure in humans. Only minor cardiovascular effects were observed at 133 ug/kg bw. The NOELs for the relevant cardiac variables were 67 ug/kg bw for electromechanical systole, ventricular ejection time, and maximum velocity of circumferential fibre shortening, 133 ug/kg bw for heart rate and 200 ug/kg bw for cardiac output.

/SIGNS AND SYMPTOMS/ Adverse effects of prolonged therapeutic use of beta-agonists including tachycardia, vasodilation, skeletal muscle tremor, nervousness, metabolic disturbances, and beta-adrenoceptor desensitization are pharmacologically predictable, dose-related and potency-related. Non-pharmacological effects include airway hyper-responsiveness and increased airway inflammation. The incidence and severity of adverse reactions may vary for any given compound. The impact of the R- and S-enantiomers of beta-agonists on adverse effects remains unclear. /beta-Agonists/

/EPIDEMIOLOGY STUDIES/ The dose-response effect of ractopamine on the human cardiovascular system was studied in a single-blind, placebo-controlled, ascending single-dose protocol. The study was conducted with six healthy male volunteers (body weight: range, 67.8-79.6 kg; mean, 75.5 kg), given oral placebo plus five oral doses of 5, 10, 15, 25, and 40 mg of ractopamine, with a washout period of 48 h between doses. On a body-weight basis, the doses ranged from 0.063 to 0.590 mg/kg bw. Using standard and echocardiographic methods, measurements for 14 cardiovascular variables were obtained at nine hourly time-points in each subject. No serious adverse events were reported. At doses of 15, 25, and 50 mg, sensations of increase in heart rate were reported for two, three, and four men, and sensation of heart pounding in one, three, and one man, respectively. The adverse effects were considered to be treatment-related and to be either mild or moderate in severity. One man was withdrawn from the study after the 25 mg dose because of adverse cardiac effects. Dose-dependent changes of cardiac variables appeared within the first hour after administration of ractopamine and gradually returned to baseline values before treatment. At a dose of 5 mg, there was apparently no cardiovascular response, and at 10 mg only minor effects were reported. At 15, 25, and 40 mg, the heart rate was elevated about 20, 30, and 50 beats per min above control and the cardiac output increased by approximately 35%, 55%, and 90%, respectively. At the same doses, the electromechanical systole was shortened by about 10%, 14%, and 19%, respectively. The systolic blood pressure increased in a dose-dependent manner. In contrast to the vasodilative effects recorded in monkeys and dogs, ractopamine did not change or even increase the diastolic pressure.

/OTHER TOXICITY INFORMATION/ The Committee concluded that the response in monkeys is more predictive of the acute cardiovascular response in humans exposed to dietary ractopamine than is that in dogs. Monitoring in the studies in animals and humans was appropriately timed to reveal the onset, time-to-peak, and duration of ractopamine-induced cardiac effects. The time course of the cardiostimulatory effects of ractopamine was comparable in humans, monkeys, and dogs.

/OTHER TOXICITY INFORMATION/ The Committee reviewed publicly available literature on nontherapeutic effects in humans after long-term use of beta-adrenoceptor agonists. The reported side-effects of prolonged therapeutic use of beta-adrenoceptor agonists include tachycardia, vasodilation, skeletal muscle tremor, nervousness, metabolic disturbances (hyperglycaemia and hypokalaemia), and beta-adrenoceptor desensitization. These effects are pharmacologically predictable, dose-related and potencyrelated, with cardiovascular effects being the most commonly reported side-effects. Non-pharmacological effects include airway hyper-responsiveness and increased airway inflammation. The incidence and severity of side-effects varies for any given compound. Tolerance to pharmacologically-predictable, non-therapeutic effects occurs readily. There is no evidence for any increased incidence of smooth muscle tumors such as leiomyomas, or of any other tumors, among human users of these drugs. Little or no relaxant response to beta2-adrenoceptor agonists has been reported for the non-pregnant human uterus.

/LABORATORY ANIMALS: Acute Exposure/ the acute cardiovascular effects or ractopamine hydrochloride were evaluated in two male and two female beagle dogs anaesthetized with pentobarbital at a dose of 30 mg/kg bw). The animals were prepared for hemodynamic monitoring and the response of pulsatile arterial pressures, pulsatile aortic flow wave forms, and left ventricular pressure to a 10-min intravenous infusion of ractopamine at 35 ug/kg bw was determined. Heart rate increased by approximately 65% during the 10-min infusion and remained elevated by at least 50% throughout the following 30-min monitoring period. Mean arterial pressure fell sharply to about 50% of its control level during the infusion and subsequently returned towards the control level, but remained depressed by approximately 25% at 40 min after infusion. The fall in mean arterial pressure was accompanied by an increase in pulse pressure as a result of the relatively greater reduction in diastolic as compared with systolic pressure. Cardiac output increased by approximately 50% during the infusion, and then stabilized at a level about 40% higher than that of controls for the next 30min. The increase in cardiac output was caused primarily by an increase in heart rate, since stroke volume only transiently increased by approximately 12% at the start of infusion and later decreased to about 82% of the control level. Total peripheral resistance fell sharply to about 35% of the control level immediately after the onset of infusion. Resistance subsequently returned to about 50% of the control level for the next 30 min. Peak aortic flow increased by approximately 90% immediately after the onset of infusion and subsequently stabilized at about 70%. The aortic flow ejection period shortened by approximately -27% during the infusion and remained shorter for the next 30 min. Changes in the time to peak flow were small and variable. The cardiac arrhythmia observed in one of the four animals could not be clearly ascribed to treatment with ractopamine or any other particular cause. The systemic cardiovascular effects included tachycardia and peripheral vasodilatation. Despite concomitant and potent augmentation of cardiac output, the magnitude of the peripheral vasodilatation was sufficient to cause a dramatic fall in mean arterial pressure. Cardiac output increased as a result of the pronounced increase in heart rate, and in spite of the decrease in left ventricular stroke volume. The decrease in stroke volume was accompanied by other changes in the aortic flow wave form consistent with an increase in left ventricular contractility. These included an increase in peak aortic flow and a reduction in the duration of the ejection period[Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 53: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ractopamine - Addendum (2004). Available from, as of July 25, 2006: http://www.inchem.org/documents/jecfa/jecmono/v53je01.htm]

/LABORATORY ANIMALS: Acute Exposure/ Groups of four male and four female beagle dogs (aged 10-19 months) were given ractopamine orally at a dose of 0, 2, 50, or 125 ug/kg bw. The lowest dose of 2 ug/kg bw was selected to be higher than the human exposure anticipated from eating 125 g of pig kidney from an animal that had not been removed from treatment with ractopamine before slaughter (zero time withdrawal). The intermediate dose of 50 ug/kg was selected because this dose had produced skin erythema without any statistically significant increase in heart rate in a previous study in dogs. The highest dose was selected because it was known to increase heart rate in this study and corresponded to the NOEL previously identified in a long-term study in monkeys. The study was designed as a double Latin square that allowed testing for residual effects and was certified for compliance with GLP and quality assurance. Left ventricular pressure, aortic blood pressure, heart rate and electrocardiograms were recorded to provide data on the effects of an oral dose of ractopamine on left ventricular function and systemic blood pressure. The peak value of the first derivative of left ventricular pressure (dP/dtmax) was used as an index of left ventricular inotropic state. Systolic, diastolic, mean aortic, and aortic pulse pressures were derived by the data acquisition system from the aortic pressure signal. Heart rate and left ventricular end-diastolic pressure were obtained from the ventricular pressure signals. All dogs survived the treatment. There was no residual carry-over effect from one treatment to the next in the Latin square design. Ractopamine caused statistically significant dose-dependent increases in heart rate and left ventricular inotropic state at 50 and 125 ug/kg bw. Maximum effects occurred approximately 2 hr after dosing with an increased heart rate of 40 and 80 beats per min at the intermediate and highest doses, respectively. Increases in left ventricular inotropy were recorded during the 6-h period after dosing. No significant change in heart rate or left ventricular inotropic state was observed at 2 ug/kg. A drop in blood pressure was evident in both the systolic and diastolic (and therefore the mean) pressures in response to treatment at 50 and 125 ug/kg during the 6-hr period immediately after dosing. Treatment at 125 ug/kg caused a decrease in aortic pulse pressure. Analysis of electrocardiograms did not indicate any treatment-related effects. Two dogs at 50 ug/kg and seven dogs at 125 ug/kg had a slight pinking of the abdominal skin (erythema). No other clinical signs were observed in the study. At 2 ug/kg, there was no significant effect on any of the parameters measured. In conclusion, treatment with ractopamine at 50 and 125 ug/kg bw caused tachycardia, an increased left ventricular inotropic state, and a fall in systemic blood pressure in dogs. The increase in heart rate was consistent with a reflex tachycardia since the increased heart rate was always accompanied by a fall in systemic in blood pressure. The results of this study are consistent with expected pharmacological effects associated with vascular beta2-adrenoceptor stimulation and subsequent vasodilation. It is possible that the increased left tachycardia and ventricular inotropy were the result of some direct effect on cardiac beta1- and beta2-adrenoceptors in the dogs. The NOEL was 2 ug/kg bw in this study[Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 53: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ractopamine - Addendum (2004). Available from, as of July 25, 2006: http://www.inchem.org/documents/jecfa/jecmono/v53je01.htm]

/LABORATORY ANIMALS: Acute Exposure/ Eight male rhesus monkeys (body weight, about 6 kg) were prepared for haemodynamic monitoring, and their response to a 10 min intravenous infusion of ractopamine at 35 ug/kg bw, as compared with an infusion of sodium chloride (NaCl), was determined in both the awake, and in the anaesthetized states. Heart rates, systolic, diastolic, and mean arterial pressures were determined from the arterial pressure wave forms. All animals survived the study, and no signs of toxicity were observed. There were no apparent effects on the hemodynamic parameters measured in response to the control infusion. In response to the infusion of ractopamine, the hemodynamic changes described below were recorded. During the conscious state, pulse pressure was increased owing to the increase in systolic pressure, which appeared virtually immediately with the onset of infusion. After the peak response approximately 8 min later, systolic pressure declined slowly to the control level over the next 90 min and was stable throughout the subsequent 6-hr monitoring period. In the anesthetized state, pulse pressure was increased by virtue of both an increase in systolic, and a decrease in diastolic pressure. The increase in systolic pressure appeared virtually immediately with the onset of infusion and continued to increase throughout the 40-min monitoring period. The decrease in diastolic pressure was shorter and less pronounced than the increase in systolic pressure. In the conscious state, heart rate increased from its control level of approximately 120 beats per min to a maximum of almost 190 beats per min by the end of the 10-min infusion. Thereafter, heart rate declined rapidly with the cessation of infusion. In the anesthetized state, despite elevated heart rate (about 150 beats per min) present before ractopamine infusion, heart rate was further increased by ractopamine to approximately 214 beats per min by the end of the 10-min infusion period. Thereafter, heart rate declined, yet it remained elevated for the duration of the 40-min monitoring period. The changes in heart rate and arterial pressures observed under anesthetized conditions were qualitatively and quantitatively similar to those previously documented for this species. These included tachycardia and slightly increased pulse and mean arterial pressure. In the conscious state, the hemodynamic responses to ractopamine infusion also resulted in tachycardia and slightly increased pulse and mean arterial pressures. Barbiturate anaesthesia appears to play an insignificant role in the modulation of hemodynamic responses to a 10-min infusion of ractopamine at 35 ug/kg bw and does not alter the qualitative acute haemodynamic response in rhesus monkeys.[Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 53: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ractopamine - Addendum (2004). Available from, as of July 25, 2006: http://www.inchem.org/documents/jecfa/jecmono/v53je01.htm]

/LABORATORY ANIMALS: Acute Exposure/ Two male and two female anesthetized rhesus monkeys (body weight, 2.5-3.5 kg; given pentobarbital at 30 mg/kg bw) were prepared for hemodynamic monitoring. The response of pulsatile arterial pressures, pulsatile aortic flow waveforms, and left ventricular pressure to a 10-min intravenous infusion of ractopamine at 35 ug/kg bw was determined. All animals survived the experimental phase of this terminal study, and no signs of toxicity were observed. Heart rate increased approximately 20% during the infusion and remained elevated throughout the 40-min monitoring period. Mean arterial pressure was maintained throughout the experiment while there was a slight augmentation of systolic pressure during the infusion. Cardiac output increased approximately 35% during the infusion and decreased steadily throughout the monitoring period. Total peripheral resistance decreased gradually to approximately -30% of its initial level during the infusion and then slowly returned towards control. Stroke volume increased approximately 14% during the infusion and exhibited a gradual return to baseline during the monitoring period. Peak aortic flow increased approximately 80% during the infusion and gradually returned toward baseline levels. The aortic flow ejection period shortened by approximately -18% during the infusion and remained so during the monitoring period. Changes in the time to peak flow were small and variable.[Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 53: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ractopamine - Addendum (2004). Available from, as of July 25, 2006: http://www.inchem.org/documents/jecfa/jecmono/v53je01.htm]

For more Non-Human Toxicity Excerpts (Complete) data for RACTOPAMINE (18 total), please visit the HSDB record page.

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

Ractopamine

Pharmaceutical

Smith, C.D. and Nowell, L.H., 2024. Health-Based Screening Levels for evaluating water-quality data (3rd ed.). DOI:10.5066/F71C1TWP

New animal drugs for use in animal feeds. Ractopamine. Conditions of use: (1) Swine: ... For increased rate of weight gain, improved feed efficiency, and increased carcass leanness in finishing swine fed a complete ration containing at least 16 percent crude protein from 150 lb (68 kg) to 240 lb (109 kg) body weight. Limitations: Feed continuously as sole ration. ... For improved feed efficiency and increased carcass leanness in finishing swine fed a complete ration containing at least 16 percent crude protein from 150 lb (68 kg) to 240 lb (109 kg) body weight. Limitations: Feed continuously as sole ration ... (2) Cattle: ... cattle fed in confinement for slaughter: For increased rate of weight gain and improved feed efficiency during the last 28 to 42 days on feed. Limitations: Feed continuously as sole ration during the last 28 to 42 days on feed. Not for animals intended for breeding. ... Cattle fed in confinement for slaughter: For increased rate of weight gain, improved feed efficiency, and increased carcass leanness during the last 28 to 42 days on feed. Limitations: Feed continuously as sole ration during the last 28 to 42 days on feed. Not for animals intended for breeding. /May be used in combination with tylosin and monesin/

New animal drugs for use in animal feeds. Requirement of a medicated feed mill license. Ractopamine is included on this list.

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Ractopamine hydrochloride is included on this list. /Ractopamine hydrochloride/

The RR-isomer (butopamine) is the stereoisomer with the most activity at the b-adrenoceptor. Butopamine was shown to be a non-selective ligand at the beta1- and beta2-adrenoceptors, but signal transduction is more efficiently coupled through the b2-adrenoceptor than the b1- adrenoceptor. Therefore, the RR-isomer of ractopamine is considered to be a full agonist at the beta2-adrenoceptor and a partial agonist at the beta-adrenoceptor. These results are consistent with the pharmacological characterization of racemic ractopamine in isolated cardiac (atria) and smooth muscle (costo-uterine, vas deferens, trachea), which shows a maximal response at beta2- and a submaximal response at b1-adrenoceptors when compared with the full beta1- and beta2- adrenoceptor agonist isoproterenol.

Elimination 1/2 life = 6-7 hours; [HSDB]

The elimination half-life was about 6-7 hr.

The results of a study in six healthy male human volunteers receiving a single oral dose of 40 mg of ractopamine hydrochloride indicate a similar profile of pharmacokinetics and biotransformation in humans and animals. ... The half-life in plasma was about 4 hr.

In urine, only a minor fraction of radioactivity recovered was parent ractopamine. Swine excreted about 4-16% of the parent compound in the urine after a single oral dose of ractopamine. After repeated doses, the amount of unchanged drug increased to 36-85% of total radioactivity in the urine collected on day 4 of a 4-day dosing regimen. In rats injected with (14)C-ractopamine at 9 mg/kg bw intraperitoneally, parent drug represented 22.6% of total urinary radioactivity while only 1.9% of radioactivity was associated with unchanged ractopamine after an oral dose of 9.9 mg/kg bw. The greater proportion of parent drug in the urine after parenteral administration than after oral administration suggests that liver and intestine play an important role in the biotransformation of ractopamine after oral administration. Therefore, although well absorbed from the gastrointestinal tract, the systemic availability of parent ractopamine is reduced, owing to a significant first-pass metabolism.

In the bile of rats dosed orally with (14)C-ractopamine, at least seven different crude metabolite fractions were partitioned chromatographically. Four of the crude metabolite fractions representing 76% of biliary radioactivity were isolated and identified with a sulfate-ester/glucuronic acid diconjugate of ractopamine as the main metabolite (46% of total biliary radioactivity). A further 6% of radioactivity was identified as a monosulfate conjugate and 25% as monoglucuronides of ractopamine. The site of sulfation was established at the C-10' phenol (aromatic ring attached to carbinol). The sulfate conjugation was not stereospecific. The major site of glucuronidation was the C-10 phenol (phenol attached to the nitrogen substituent).

After a withdrawal of 6 hr (rats, dogs) or 12hr (swine, cattle), unchanged ractopamine represented 40, 14, 52, and 13-16% of the total extractable and identifiable residues in the rat, dog, pig, and cattle livers, respectively, and 21, 29, 28-30, and 14% in the kidneys, respectively. After a withdrawal of 24 hr and 72 hr, parent ractopamine represented 14.1% and 3.6% in liver, and 27.5% and 3% of total residues in kidney, respectively, in swine. The remaining residue was found to comprise conjugates of ractopamine. The chromatographic profiles of the (14)C-labelled residue extracts of rat, dog, pig, and cattle liver were qualitatively similar. The laboratory animals had generally a higher percentage of metabolites as residues. Studies in rats and dogs showed that urine from animals dosed with (14)C-ractopamine contained the same four glucuronide metabolites of ractopamine as in pigs. It is concluded that the dogs and rats used in the toxicological studies were exposed to the same metabolites as those found in the edible tissues of pigs and cattle.

In studies in rats, dogs, pigs, and cattle fed (14)C-ractopamine, a fourth metabolite was identified as a glucuronic acid diconjugate. The conjugation of the hydroxyl groups in both the aromatic ring attached to the carbinol and the phenol attached to the nitrogen substituent was not stereospecific.

For more Metabolism/Metabolites (Complete) data for RACTOPAMINE (8 total), please visit the HSDB record page.

/The authors/ investigated the detection, confirmation, and metabolism of the beta-adrenergic agonist ractopamine administered as Paylean to the horse. ... Based on the quantitation ions for ractopamine standards extracted from urine, standard curves showed a linear response for ractopamine concentrations between 10 and 100 ng/mL with a correlation coefficient r > 0.99, whereas standards in the concentration range of 10-1000 ng/mL were fit to a second-order regression curve with r > 0.99. ... Urine concentration of parent ractopamine 24 h post-dose was measured at 360 ng/mL by GC-MS after oral administration of 300 mg. Urinary metabolites were identified by electrospray ionization (+) tandem quadrupole mass spectrometry and were shown to include glucuronide, methyl, and mixed methyl-glucuronide conjugates

In a bioavailability study that complied with good laboratory practice (GLP), groups of five male and five female rats were given [14C]ractopamine as a single oral dose at 0.5, 2.0, or 20 mg/kg bw by gavage. The amount of radiolabel was quantified in samples of plasma and whole blood collected for 24 hr after dosing. Comparison of the area under the curve (AUC) of concentration-time for plasma and whole blood indicated that the bioavailability of (14)C-ractopamine was proportional to dose for males and females at doses up to 2.0 mg/kg bw. Increasing the dose to 20 mg/kg bw resulted in an increase in AUC versus dose in males and, to a more pronounced degree, in females. The absolute bioavailability of (14)C-ractopamine in rats cannot be determined from the results of this study since (14)C-ractopamine was not administered intravenously for comparison of oral and intravenous AUC values.

Experiments were conducted to determine the total residues remaining in ocular tissues of cattle and turkeys after oral administration of (14)C-ractopamine HCl. Twelve cattle were intraruminally dosed with 0.9 mg /kg/d of (14C-)ractopamine HCl for 7 d. Four cattle each were slaughtered with withdrawal periods of 48, 96, and 144 hr. Radioactive residues were not detectable in whole-eye homogenates from the cattle. Eight male and eight female turkeys per treatment received either 7.5, 22.5, or 30 ppm dietary (14)C-ractopamine HCl (0.33, 1.02, and 1.36 mg/kg/d; treatment groups 1, 2, and 3, respectively) for 7 d, and the birds were slaughtered with a 0-d withdrawal period. Eyes were dissected into retina/choroid/schlera (RCS), cornea/iris (CI), and aqueous humor (AH) fractions. Residues in RCS, CI, and AH of treatment 1 turkeys were not detectable. Residues in AH were < 0.02 ppm in treatment groups 2 and 3. Mean residues in RCS ranged from 0.15 to 0.26 ppm, and mean CI residues ranged from <0.09 to 0.17 ppm for treatment groups 2 and 3, respectively.

Ractopamine HCl is a beta-adrenergic leanness-enhancing agent recently approved for use in swine. Depletion of ractopamine in tissues, and elimination of ractopamine and its metabolites in urine, is of interest for the detection of off-label use. The objectives of this study were to measure the residues of ractopamine in livers and kidneys of cattle (n = 6), sheep (n = 6), and ducks (n = 9) after treatment with dietary ractopamine for seven (sheep, ducks) or eight (cattle) consecutive days and to measure the depletion of ractopamine from urine of cattle and sheep. Two cattle and sheep and three ducks were each slaughtered with withdrawal periods of 0, 3, and 7 day. Urine samples were collected daily from cattle and sheep. Tissue ractopamine concentrations were determined using the regulatory method (FDA approved) for ractopamine in swine tissues. Ractopamine residues in urine samples were measured before and after hydrolysis of conjugates. Analysis was performed with HPLC using fluorescence detection after liquid- (hydrolyzed samples) and(or) solid-phase extraction. No residues were detected in duck tissues. Liver residues in sheep averaged 24.0 and 2.6 ppb after 0- and 3-day withdrawal periods, respectively. Sheep liver residues after a 7-day withdrawal period were less than the limit of quantification (2.5 ppb). Sheep kidney residues were 65.1 and undetectable at 0- and at 3- and 7-day, withdrawal periods, respectively. Cattle liver residues were 9.3, 2.5, and undetectable after 0-, 3-, and 7-day withdrawal periods, respectively; kidney residues were 97.5, 3.4, and undetectable at the same respective withdrawal periods. Concentrations of parent ractopamine in sheep urine were 9.8+ or - 3.3 ppb on withdrawal d 0 and were below the LOQ (5 ppb) beyond the 2-day withdrawal period. After the hydrolysis of conjugates, ractopamine concentrations were 5,272 + or - 1,361 ppb on withdrawal d 0 and 178 + or - 78 ppb on withdrawal d 7. Ractopamine concentrations in cattle urine ranged from 164+ or - 61.7 ng/mL (withdrawal d 0) to below the LOQ (50 ppb) on withdrawal day 4. After the hydrolysis of conjugates in cattle urine, ractopamine concentrations were 4,129+ or - 2,351 ppb (withdrawal day 0) to below the LOQ (withdrawal d 6). These data indicate that after the hydrolysis of conjugates, ractopamine should be detectable in urine of sheep as long as 7 day after the last exposure to ractopamine and as long as 5 day after withdrawal in cattle.

For more Absorption, Distribution and Excretion (Complete) data for RACTOPAMINE (16 total), please visit the HSDB record page.

Used to promote animal growth and enhance carcass leanness of swine; [Merck Index]

Farming (Pesticides) [Category: Industry]

Mesh Heading: Adrenergic beta-agonists

MEDICATION (VET)

MEDICATION (VET): Ractopamine HCl is an beta-adrenergic receptor (betaAR) ligand that was recently approved for use in swine to enhance carcass leanness.