Metabolism of the analgesic drug, tramadol hydrochloride, in rat and dog

Wu, W. N.; McKown, Linda A.; Gauthier, Annick; Jones, Walter W.; Raffa, Robert B.

doi:10.1080/00498250110057378

Cited by 97 publications

(80 citation statements)

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“…The plasma concentrations of tramadol and M1 in our dogs were a little higher than those in awaking dogs [15,18]. Tramadol is metabolized in the liver, and its metabolites primarily were excreted via the kidneys (90%) with the remaining (10%) being excreted via feces [25,29]. In addition, volatile inhalation anesthetics including sevoflurane cause a dose-dependent cardio-pulmonary depression in dogs [27].…”

Section: Discussionmentioning

confidence: 99%

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Effects of a Single Bolus Intravenous Dose of Tramadol on Minimum Alveolar Concentration (MAC) of Sevoflurane in Dogs

Itami

Kawase

Tamaru

et al. 2013

The Journal of Veterinary Medical Science

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ABSTRACT. Tramadol is an atypical opioid analgesic widely used in small animal practice. This study was designed to determine the effect of a single intravenous (IV) dose of tramadol on the minimum alveolar concentration (MAC) of sevoflurane in dogs. Six beagle dogs were anesthetized twice to determine the sevoflurane MAC with or without an administration of tramadol (4 mg/kg, IV) at 7 days interval. The sevoflurane MAC was determined using a tail clamp method in each dog ventilated with positive pressure ventilation. The tramadol administration produced a significant reduction in the sevoflurane MAC by 22.3 ± 12.2% (1.44 ± 0.28% with tramadol versus 1.86 ± 0.30% without tramadol, P=0.010). This MAC reduction had been determined from 122 ± 19 to 180 ± 41 min following the tramadol administration. During this period, the plasma concentrations of tramadol and its metabolite, O-desmethyltramadol (M1), decreased from 429 ± 64 to 332 ± 55 ng/ml and from 136 ± 24 to 114 ± 68 ng/ml, respectively, but these changes were not statistically significant. There was no significant difference in heart rate, mean arterial blood pressure and SpO 2 between the control and tramadol treatment. The dogs that received tramadol treatment sometimes breathed spontaneously. Therefore, their respiratory rates significantly increased, and PETCO 2 decreased during the MAC determination. In conclusion, the single IV dose of tramadol produced a significant reduction in the sevoflurane MAC in dogs.

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Section: Discussionmentioning

confidence: 99%

“…One of the metabolites from tramadol, O-desmethyltramadol (M1), also has a weak µ agonist effect and has up to 200 times more µ-opioid receptor binding activity than tramadol [8,9,24]. M1 may be playing a part of the anti-nociceptive effects of tramadol, because its production from the parent compound has been demonstrated in dogs [15,29].…”

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Effects of a Single Bolus Intravenous Dose of Tramadol on Minimum Alveolar Concentration (MAC) of Sevoflurane in Dogs

Itami

Kawase

Tamaru

et al. 2013

The Journal of Veterinary Medical Science

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“…M1 has a 200 times higher μ-opioid receptor binding activity than tramadol [8,25] and its formation is important for the anti-nociceptive effects of tramadol [24]. In dogs, M1 production from the parent compound has been also demonstrated [11,33]. Therefore, M1 probably contributes to anti-nociceptive effects of tramadol in dogs.…”

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confidence: 99%

Cardiovascular Effects of Tramadol in Dogs Anesthetized with Sevoflurane

Itami

Tamaru

Kawase

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. Cardiovascular effects of tramadol were evaluated in dogs anesthetized with sevoflurane. Six beagle dogs were anesthetized twice at 7 days interval. The minimum alveolar concentration (MAC) of sevoflurane was earlier determined in each dog. The dogs were then anesthetized with sevoflurane at 1.3 times of predetermined individual MAC and cardiovascular parameters were evaluated before (baseline) and after an intravenous injection of tramadol (4 mg/kg). The administration of tramadol produced a transient and mild increase in arterial blood pressure (ABP) (P=0.004) with prolonged increase in systemic vascular resistance (SVR) (P<0.0001). Compared with baseline value, mean ABP increased significantly at 5 min (119% of baseline value, P=0.003), 10 min (113%, P=0.027), and 15 min (111%, P=0.022). SVR also increased significantly at 5 min (128%, P<0.0001), 10 min (121%, P=0.026), 30 min (114%, P=0.025), 45 min (113%, P=0.025) and 60 min (112%, P=0.048). Plasma concentrations of tramadol were weakly correlated with the percentage changes in mean ABP (r=0.642, P<0.0001) and SVR (r=0.646, P<0.0001). There was no significant change in heart rate, cardiac output, cardiac index, stroke volume, pulmonary arterial pressure, right atrial pressure and pulmonary capillary wedge pressure.In conclusion, the administration of tramadol produces a prolonged peripheral vascular constriction in dogs anesthetized with sevoflurane, which is accompanied with a transient and mild increase in arterial blood pressure. It also indicated that the degree of vasoconstriction might depend on the plasma concentration of tramadol.KEY WORDS: canine, cardiovascular effects, sevoflurane, tramadol.J. Vet. Med. Sci. 73(12): 1603-1609, 2011 Treatment with analgesic drugs reduces the amount of anesthetics required to produce surgical anesthesia, helps to stabilize anesthesia, and decreases overall patient morbidity associated with surgery and anesthesia [17]. Opioid administration decreases the amount of volatile anesthetics required to produce general anesthesia, as evidenced by decreases in the minimum alveolar concentration (MAC) of volatile anesthetics [10,19].Tramadol is a centrally acting 'atypical' opioid analgesic and widely used in humans for control of acute and chronic pain [6,25]. Tramadol is less likely to induce tolerance in animals and humans compared with morphine because of its non-opioid mechanism of action [15]. Use of tramadol in dogs has gained popularity among veterinarians because the drug is perceived to be an effective analgesic, in easily administered, and has a longer duration of action and fewer adverse effects than most other opioids. It was demonstrated that tramadol administration decreased in the MAC of volatile anesthetics [28] and its preoperative administration provided an early pain control after ovariohysterectomy in dogs [13]. Tramadol produces a synergistic analgesic effect provided by a μ-opioid receptor affinity coupled with inhibitions of synaptic reuptake of monoamine neurotransmitters such as 5-hydroxyt...

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“…In an organism it is preferentially metabolized by O-and N-desmethylation to O-desmethyl-(M1) and N,N-didesmethyltramadol (M3). Also other metabolites of tramadol, which occur in rat and in dog, were elucidated with the aid of MS [11]. Three major metabolites M1, M3, M5 were chosen for our study.…”

Section: Introductionmentioning

confidence: 99%

Comparison of different stationary phases for bioanalytical studies of biologically active compounds

Zerzaňová¹,

Cisar

Klimeš

2006

J. Sep. Sci.

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In this study, the chromatographic behaviour of four mixtures of compounds was tested on columns possessing various surface properties. Cocaine, dimefluron, nabumetone, and tramadol were chosen as the test compounds. Cocaine is a tropane alkaloid, which is relatively often abused as a drug. This is why many papers have already been written about its determination in human biological samples. Dimefluron, a derivative of benzo[c]fluorene, is a new perspective drug being investigated for its potential antineoplastic effects. Nabumetone is a non-steroidal anti-inflammatory prodrug used for treatment of inflammatory and degenerative rheumatic diseases. Tramadol, derived from an opioid structure is used as an anodyne for treatment of severe pain. As a medicament it is usually determined either in biological samples or in pharmaceuticals. The above-mentioned model drugs were separated using chromatographic columns with C18, C8, palmitamidopropyl, and pentafluorophenylpropyl chains. The best conditions for separation of the individual compounds and their metabolites were chosen on the basis of resolution, retention times, and peak symmetry.

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Metabolism of the analgesic drug, tramadol hydrochloride, in rat and dog

Cited by 97 publications

References 4 publications

Effects of a Single Bolus Intravenous Dose of Tramadol on Minimum Alveolar Concentration (MAC) of Sevoflurane in Dogs

Effects of a Single Bolus Intravenous Dose of Tramadol on Minimum Alveolar Concentration (MAC) of Sevoflurane in Dogs

Cardiovascular Effects of Tramadol in Dogs Anesthetized with Sevoflurane

Comparison of different stationary phases for bioanalytical studies of biologically active compounds

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