J. E. Ilkiw

Pharmacokinetics of tramadol, and its metabolite O-desmethyl-tramadol, in cats

Tramadol is an analgesic agent and is used in dogs and cats. Tramadol exerts its action through interactions with opioid, serotonin and adrenergic receptors. The opioid effect of tramadol is believed to be, at least in part, related to its metabolite, O-desmethyl-tramadol. The pharmacokinetics of tramadol and O-desmethyl-tramadol were examined after intravenous (i.v.) and oral administration of tramadol to six cats. A two-compartment model (with first-order absorption in the central compartment for the oral administration) with elimination from the central compartment best described the disposition of tramadol in cats. After i.v. administration, the apparent volume of distribution of the central compartment, the apparent volume of distribution at steady-state, the clearance, and the terminal half-life (mean +/- SEM) were 1553+/-118 mL/kg, 3103+/-132 mL/kg, 20.8+/-3.2 mL/min/kg, and 134+/-18 min, respectively. Systemic availability and terminal half-life after oral administration were 93+/-7% and 204+/-8 min, respectively. O-desmethyl-tramadol rapidly appeared in plasma following tramadol administration and had terminal half-lives of 261+/-28 and 289+/-19 min after i.v. and oral tramadol administration, respectively. The rate of formation of O-desmethyl-tramadol estimated from a model including both tramadol and O-desmethyl-tramadol was 0.014+/-0.003/min and 0.004+/-0.0008/min after i.v. and oral tramadol administration, respectively.

Effect of amantadine on oxymorphone-induced thermal antinociception in cats

This study examined the effect of amantadine, an N-methyl-d-aspartate receptor antagonist, on the thermal antinociceptive effect of oxymorphone in cats. Six adult healthy cats were used. After baseline thermal threshold determinations, oxymorphone was administered intravenously to maintain plasma oxymorphone concentrations of 10, 20, 50, 100, 200, and 400 ng/mL. In addition, amantadine, or an equivalent volume of saline, was administered intravenously to maintain a plasma amantadine concentration of 1100 ng/mL. Thermal threshold and plasma oxymorphone and amantadine concentrations were determined at each target plasma oxymorphone concentration. Effect maximum models were fitted to the oxymorphone concentration-thermal threshold data, after transformation in % maximum response. Oxymorphone increased skin temperature, thermal threshold, and thermal excursion (i.e., the difference between thermal threshold and skin temperature) in a concentration-dependent manner. No significant difference was found between the amantadine and saline treatments. Mean ± SE oxymorphone EC(50) were 14.2 ± 1.2 and 24.2 ± 7.4 ng/mL in the amantadine and saline groups, respectively. These values were not significantly different. Large differences in oxymorphone EC(50) in the saline and amantadine treatment groups were observed in two cats. These results suggest that amantadine may decrease the antinociceptive dose of oxymorphone in some, but not all, cats.

Effect of dexmedetomidine on the minimum alveolar concentration of isoflurane in cats

This study reports the effects of dexmedetomidine on the minimum alveolar concentration of isoflurane (MAC(iso) ) in cats. Six healthy adult female cats were used. MAC(iso) and dexmedetomidine pharmacokinetics had previously been determined in each individual. Cats were anesthetized with isoflurane in oxygen. Dexmedetomidine was administered intravenously using target-controlled infusions to maintain plasma concentrations of 0.16, 0.31, 0.63, 1.25, 2.5, 5, 10, and 20 ng/mL. MAC(iso) was determined in triplicate at each target plasma dexmedetomidine concentration. Blood samples were collected and analyzed for dexmedetomidine concentration. The following model was fitted to the concentration-effect data: [Formula in text] where MAC(iso.c) is MAC(iso) at plasma dexmedetomidine concentration C, MAC(iso.0) is MAC(iso) in the absence of dexmedetomidine, I(max) is the maximum possible reduction in MAC(iso), and IC(50) is the plasma dexmedetomidine concentration producing 50% of I(max). Mean ± SE MAC(iso.0), determined in a previous study conducted under conditions identical to those in this study, was 2.07 ± 0.04. Weighted mean ± SE I(max), and IC(50) estimated by the model were 1.76 ± 0.07%, and 1.05 ± 0.08 ng/mL, respectively. Dexmedetomidine decreased MAC(iso) in a concentration-dependent manner. The lowest MAC(iso) predicted by the model was 0.38 ± 0.08%, illustrating that dexmedetomidine alone is not expected to result in immobility in response to noxious stimulation in cats at any plasma concentration.

Effect of dexmedetomidine on its clearance: a pharmacokinetic model

Department of Surgical and Radiological Sciences School of Veterinary Medicine University of California, Davis, CA

Anesthetic management in feline renal transplantation

OBJECTIVE To document perioperative and anesthetic management of 30 feline renal transplant recipients (1996-1998). STUDY DESIGN Retrospective clinical study. ANIMALS Thirty adult cats in end-stage renal failure that underwent heterotopic renal transplantation. MATERIALS AND METHODS The medical records were reviewed from 30 feline heterotopic renal transplant recipients. Cases were included only if they had been treated for hypertension using a beta-adrenergic antagonist, a calcium channel blocker or hemodialysis. Data regarding signalment, preoperative management, surgical technique, type and doses of anesthetics administered, perioperative hemodynamics and intra- and postoperative complications, postoperative analgesia, morbidity and early mortality were recorded. Data were expressed as mean ± SD. RESULTS Preanesthetic medication included a combination of an anticholinergic and an opioid (oxymorphone). Anesthesia induction was performed mostly with isoflurane and oxygen delivered by mask. Anesthesia maintenance was primarily achieved with isoflurane in 100% oxygen. Nitrous oxide was often used as part of the anesthetic technique. The mean duration of anesthesia was 4.6 hours ± 27 minutes. The mean renal allograft ischemic time was 60 minutes. During the anesthetic period, the majority of the recipient cats received either fresh whole blood (FWB) (N = 25, 83%), cross-matched packed red blood cells (PRBC) (N = 3, 10%) or fresh frozen plasma (FFP) (N = 2, 7%) combined with a balanced electrolyte solution. Blood products administered averaged 63 ± 34 mL and crystalloid 94 ± 62 mL. The most common treated intraoperative complications were hypotension (N = 14, 47%), hypothermia (N = 13, 43%), metabolic acidosis (N = 11, 37%), hypocalcemia (N = 5, 17%), hypoglycemia (N = 4, 13%), hypertension (N = 2, 7%), bradycardia (N = 1, 3%), and ventricular premature contractions (N = 1, 3%). All cats received opioid analgesics postoperatively. Complications observed in the first 24 hours postoperatively were hypertension (N = 20, 67%), hematuria (N = 14, 47%), electrolyte disturbances (N = 9, 30%), temperature imbalances (N = 5, 17%), decreased PCV requiring blood transfusion (N = 5, 17%), decreased perfusion of a foot associated with external iliac anastomosis technique (N = 5, 17%), seizures associated with hypertension (N = 3, 10%), uroabdomen (N = 2, 7%), acute graft rejection (N = 1, 3%) and, corneal ulceration (N = 1, 3%). Survival rates in the perioperative period were 100, 96.7, and 93.4% intraoperatively, at 24 hours, and 7 days following surgery. CONCLUSION Successful anesthesia can be performed in critically ill renal transplant recipients. However, for optimal graft function and patient survival, normothermia, normovolemia, normotension, and normal acid-base and electrolyte balance should be carefully maintained. Successful anesthetic management requires understanding of the pathophysiology of end-stage renal disease and the maintenance of homeostasis during the different stages of the perioperative period.

Pharmacokinetics of oxymorphone in cats.

This study reports the pharmacokinetics of oxymorphone in spayed female cats after intravenous administration. Six healthy adult domestic shorthair spayed female cats were used. Oxymorphone (0.1 mg/kg) was administered intravenously as a bolus. Blood samples were collected immediately prior to oxymorphone administration and at various times up to 480 min following administration. Plasma oxymorphone concentrations were determined by liquid chromatography-mass spectrometry, and plasma oxymorphone concentration-time data were fitted to compartmental models. A three-compartment model, with input in and elimination from the central compartment, best described the disposition of oxymorphone following intravenous administration. The apparent volume of distribution of the central compartment and apparent volume of distribution at steady state [mean ± SEM (range)] and the clearance and terminal half-life [harmonic mean ± jackknife pseudo-SD (range)] were 1.1 ± 0.2 (0.4-1.7) L/kg, 2.5 ± 0.4 (2.4-4.4) L/kg, 26 ± 7 (18-38) mL/min.kg, and 96 ± 49 (62-277) min, respectively. The disposition of oxymorphone in cats is characterized by a moderate volume of distribution and a short terminal half-life.