Investigation of the interaction between buprenorphine and sufentanil during anaesthesia for ovariectomy in dogs

OBJECTIVE: To investigate the effect of buprenorphine pre-treatment on sufentanil requirements in female dogs undergoing ovariectomy. STUDY DESIGN: Randomized, 'blinded', prospective clinical study. ANIMALS: Thirty healthy female dogs referred for ovariectomy. MATERIALS AND METHODS: Dogs were randomly assigned to one of two pre-anaesthetic treatment groups. Those in the buprenorphine group (B) received buprenorphine 20 microg kg(-1) and acepromazine 0.03 mg kg(-1) IM. Control group (C) animals received an equal volume of NaCl 0.9% and acepromazine 0.03 mg kg(-1) IM. The anaesthetic technique was identical in both groups. Pre-anaesthetic medication consisted of intravenous (IV) sufentanil (1.0 microg kg(-1)) and midazolam (0.05 mg kg(-1)) and intramuscular atropine (0.03 mg kg(-1)). Anaesthesia was induced with propofol and maintained with a constant rate infusion of sufentanil (1.0 microg kg(-1) hour(-1)) and with oxygen-isoflurane. Ventilation was controlled mechanically. Ovariectomy was performed using a standard technique. Baseline heart rate (HR) and direct mean arterial blood pressure (MAP) were recorded before the first incision. Increases in HR and MAP of > or =20% over baseline and, or spontaneous ventilation were controlled using IV sufentanil (1.0 microg kg(-1)) repeated after 5 minutes if haemodynamic variables remained elevated or attempts at spontaneous ventilation persisted. Analysis of variance was used to determine group differences in mean and median HR and MAP and to compare the maximum HR and MAP attained during surgery. Poisson regression was used to compare the number of sufentanil injections required in both groups. RESULTS: Group B required 2.46 times more sufentanil injections (p = 0.00487) than dogs in group C to maintain haemodynamic stability and prevent spontaneous ventilation during surgery. Group B dogs also had a significantly higher (p = 0.034) marginal mean of the log maximum MAP (4.756 +/- 0.036) compared with group C (4.642 +/- 0.036). CONCLUSIONS: Pre-treatment with buprenorphine appears to negatively influence the antinociceptive efficacy of intra-operative sufentanil. CLINICAL RELEVANCE: Withholding buprenorphine therapy 6-8 hours before anaesthesia incorporating pure mu receptor agonists is probably advisable. Alternative methods of analgesia should be provided in this period.     

Cardiopulmonary, anesthetic, and postanesthetic effects of intravenous infusions of propofol in greyhounds and non-greyhounds.

The cardiopulmonary, anesthetic, and postanesthetic effects of an IV infusion of the hypnotic agent propofol were assessed in 6 Greyhounds and 7 non-Greyhounds. After IM injection of acetylpromazine and atropine, a bolus injection of propofol sufficient to allow endotracheal intubation (mean +/- SEM = 4.0 +/- 0.3 mg/kg of body weight in Greyhounds; 3.2 +/- 0.1 mg/kg in non-Greyhounds) was administered, followed by continuous infusion at a rate of 0.4 mg/kg/min for 60 minutes, during which time dogs breathed 100% oxygen. In 23% of all dogs (3 of 13), apnea developed after initial bolus administration of propofol. Arterial blood pressure was well maintained in all dogs, but heart and respiratory rates were decreased significantly (P less than 0.05) during the infusion in Greyhounds. In Greyhounds, mild respiratory acidosis developed after 45 minutes, whereas arterial carbon dioxide tension was increased at all times after propofol administration in non-Greyhounds. In all dogs, PCV and total plasma proteins were unaffected by propofol. Rectal temperature decreased during treatment. Muscle tremors were observed in approximately 50% of dogs (in 3 of 6 Greyhounds and 3 of 7 non-Greyhounds) during and after infusion of propofol. Non-Greyhounds lifted their heads, assumed sternal recumbency, and stood 10 +/- 1, 15 +/- 3, and 28 +/- 5 minutes, respectively, after the end of the infusion; in Greyhounds, the corresponding times were 36 +/- 4, 43 +/- 6, and 63 +/- 7 minutes.     

Intravenous administration of lenperone and glycopyrrolate followed by continuous infusion of sufentanil in dogs: cardiovascular effects

Cardiopulmonary effects of IV administration of lenperone (0.44 mg/kg) and glycopyrrolate (0.11 mg/kg) were determined in 6 healthy adult (2 to 5 years) Pointers during controlled ventilation with oxygen. Sufentanil was then administered as a loading dose (5 micrograms/kg, IV) and continually infused (0.1 microgram/kg/min) for 120 minutes. Lenperone-glycopyrrolate did not significantly affect heart rate, but induced a significant decrease in systemic vascular resistance, rate-pressure product, and mean arterial pressure, and significantly increased cardiac index. Administration of sufentanil did not significantly affect mean arterial pressure. Heart rate and rate-pressure product were significantly decreased during sufentanil infusion. Systemic vascular resistance gradually increased during the 2-hour sufentanil infusion and was not significantly different from base-line values at end of study. Cardiac index was not significantly different from baseline values during sufentanil infusion, except at 90 and 120 minutes, when it was significantly less. As administered in the present study, lenperone, glycopyrrolate, and sufentanil are safe and efficacious in adult dogs.     

Long-term anaesthesia with propofol and alfentanil in the dog and its partial reversal with nalbuphine

Prolonged surgical anaesthesia in the dog was induced with propofol (6.5 ± 1.3 mg/kg) followed by alfentanil (25.5 ± 5 μg/kg) (mean ± 1 sd) and maintained with a continuous infusion of propofol (0.14 to 0.18 mg/kg/min) and alfentanil (2 to 3 μg/kg/min). Neuromuscular blockade was produced with vecuronium (0.1 mg/kg). After induction of anaesthesia with propofol, administration of alfentanil to dogs which had received no pre-anaesthetic medication produced cardiac arrest and apnoea. Administration of atropine intravenously immediately prior to alfentanil prevented these cardiac depressant effects. The cardiac depressant effect of alfentanil was not as severe in a second group of dogs in which anaesthesia was induced with thiopentone. After commencing the continuous infusion anaesthetic regime and establishment of IPPV, blood pressure and heart rate remained stable during the remaining 4 to 6 h period of anaesthesia. Recovery from anaesthesia was smooth and uneventful. The depressant effects of alfentanil on respiration and on consciousness were reversed rapidly by administration of nalbuphine (10 mg total dose). The smooth recovery and the integration of anaesthesia and post operative analgesia attained by the reversal of alfentanil with nalbuphine make this an attractive anaesthetic regime for major surgery in dogs, provided that facilities for IPPV are available.     

Effect of marbofloxacin on cardiovascular variables in healthy isoflurane-anesthetized dogs

OBJECTIVE: To study the hemodynamic effects of marbofloxacin (MBF) in isoflurane-anesthetized dogs. ANIMALS: 6 healthy 8-month-old Beagles. PROCEDURE: Anesthesia was induced with sodium thiopental and maintained with isoflurane. Cardiovascular variables were monitored throughout anesthesia. Marbofloxacin was administered by an IV bolus at 2 mg/kg, followed 10 minutes later by an infusion at a rate of 40 mg/kg/h for 30 minutes (total dose, 20 mg/kg). Plasma MBF concentrations were measured by high-performance liquid chromatography. RESULTS: The mean peak concentration during MBF infusion was 34.2 +/- 6.4 microg/mL. The IV administration of the MBF bolus did not alter any cardiovascular variable in isoflurane-anesthetized dogs. Significant changes were found during infusion when a cumulative dose of 12 mg/kg had been given. The maximal decreases observed at the end of the infusion were 16% in heart rate, 26% in systolic left ventricular pressure, 33% in systolic aortic pressure, 38% in diastolic aortic pressure, 29% in cardiac output, and 12% in QT interval. All dogs recovered rapidly from anesthesia at the end of the experiment. CONCLUSIONS AND CLINICAL RELEVANCE: MBF may safely be used at 2 mg/kg IV in isoflurane-anesthetized dogs, and significant adverse cardiovascular effects are found only when 6 to 8 times the recommended dose is given.     

SUFENTANIL-MIDAZOLAM ANAESTHESIA IN THE DOG

An anaesthetic protocol consisting of a mixture of the potent opiate sufentanil (Sufenta®, Janssen Pharmaceuticals) and the benzodiazepine midazolam (Dormicum®, Hoffmann-LaRoche) in combination with artificial ventilation with 0₂/air or 0₂/N₂0 was developed for the canine patient with a decreased cardiovascular reserve. The clinical applicability and haemodynamic stability of the sufentanil/midazolam mixture was investigated in patients admitted for surgery on account of a gastric dilatation/volvulus. A smooth and easy induction was obtained by IV sufentanil/midazolam dosed to effect, without previous premedication. A mean infusion rate of 3 ± 0.4 γg/kg/hovr sufentanil in combination with 0.9 ± 0.1 mg/kg/hour midazolam was needed for maintenance of anaesthesia. All animals were ventilated to an end-tidal C0₂% between 4.0–5.0%. All patients demonstrated great haemodynamic stability, with only a sporadic occurrence of ventricular ectopic beats. At the end of surgery, buprenorphine was administered to all animals IV. During the recovery period no untoward signs could be detected, and all animals regained spontaneous ventilatory movement as well as consciousness, without any complication.     

COMPARISON OF CARDIOPULMONARY RESPONSES TO DETOMIDINE ADMINISTERED AS AN INTRAVENOUS STEADY-STATE INFUSION VS INTRAVENOUS BOLUS IN STANDING HORSES

We compared the cardiopulmonary response to detomidine (DET) administered to two different groups of horses after IV steady-state infusion (n = 7) or IV bolus (n = 6) at similar plasma DET concentrations. Based upon previously reported kinetics, a computer predicted DET plasma concentrations and controlled an infusion pump which maintained steady-state arterial plasma DET for the infusion studies. These pharmacokinetics were used to estimate DET plasma concentrations at measurement times following IV bolus DET in the second group of horses. Cardiopulmonary measurements were made following 15 minutes of steady-state infusion and 30 minutes after IV bolus of DET. DET plasma concentration was estimated to be similar between A), 19 ng DET/ml plasma infusion and 30 minutes following an IV bolus dose of 10 γg DET/kg, (estimated plasma concentration 20.5 ng/ml), and B), 43 ng DET/ml plasma infusion and 30 minutes following an IV bolus of 20 γg DET/kg (estimated plasma concentration 42 ng/ml).     

Comparison of the effects of morphine administered by constant-rate intravenous infusion or intermittent intramuscular injection in dogs

OBJECTIVE: To compare physiologic and analgesic effects of morphine when given by IV constant-rate infusion or by IM injection to dogs undergoing laparotomy and to determine pharmacokinetics of morphine in dogs following IV constant-rate infusion. DESIGN: Prospective randomized controlled trial. ANIMALS: 20 dogs. PROCEDURE: Dogs undergoing laparotomy were treated with morphine beginning at the time of anesthetic induction. Morphine was administered by IV infusion (0.12 mg/kg/h [0.05 mg/lb/h] of body weight) or by IM injection (1 mg/kg [0.45 mg/lb]) at induction and extubation and every 4 hours thereafter. Treatments continued for 24 hours after extubation. RESULTS: Blood gas values did not indicate clinically significant respiratory depression in either group, and degree of analgesia (determined as the University of Melbourne Pain Scale score) and incidence of adverse effects (panting, vomiting, defecation, and dysphoria) were not significantly different between groups. Dogs in both groups had significant decreases in mean heart rate, rectal temperature, and serum sodium and potassium concentrations, compared with preoperative values. Mean +/- SEM total body clearance of morphine was 68 +/- 6 ml/min/kg (31 +/- 3 ml/min/lb). Mean steady-state serum morphine concentration in dogs receiving morphine by constant-rate infusion was 30 +/- 2 ng/ml. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that administration of morphine as a constant-rate IV infusion at a dose of 0.12 mg/kg/h induced effects similar to those obtained with administration at a dose of 1 mg/kg, IM, every 4 hours in dogs undergoing laparotomy. Panting was attributed to an opioid-induced resetting of the hypothalamic temperature set point, rather than respiratory depression.     

Intramuscular, intravenous and oral levetiracetam in dogs: safety and pharmacokinetics

Intravenous (IV) levetiracetam (LEV) is available for humans for bridge therapy when the oral route is unavailable. We investigated the safety and pharmacokinetics of LEV administered intramuscularly (IM), IV, and orally to dogs.
Six Hound dogs received 19.5–22.6 mg/kg of LEV IM, IV and orally with a wash-out period in between. All dogs received 500 mg LEV orally and 5 mL of 100 mg/mL LEV IM. Three dogs received 500 mg of LEV IV and three dogs received 250 mg LEV IV with 250 mg given perivascularly to approximate extravasation. Safety was assessed using a pain scale at time of IM administration and histopathological examination 24 h to 5 days after injection.
Intravenous LEV half-life was 180 ± 18 min. Bioavailability of IM LEV was 100%. Mean time to T_max after IM was 40 ± 16 min. The mean C_max IM was 30.3 ± 3 μg/mL compared to the C₀ of 37 ± 5 μg/mL for IV. Mean inflammation score (0–4 scale) for IM LEV was 0.28 and for saline 0.62. Extravasation did not cause tissue damage.
Parenteral LEV is well tolerated and appears safe following IM and IV injections in dogs. Parenteral LEV should be evaluated for use in dogs with epilepsy.     

Pharmacokinetics of ceftazidime in dogs following subcutaneous administration and continuous infusion and the association with in vitro susceptibility of Pseudomonas aeruginosa

OBJECTIVE: To determine the pharmacokinetics of ceftazidime following subcutaneous administration and continuous IV infusion to healthy dogs and to determine the minimum inhibitory concentration (MIC) of ceftazidime for clinical isolates of Pseudomonas aeruginosa. ANIMALS: 10 healthy adult dogs. PROCEDURE: MIC of ceftazidime for 101 clinical isolates of P aeruginosa was determined in vitro. Serum concentrations of ceftazidime were determined following subcutaneous administration of ceftazidime (30 mg/kg of body weight) to 5 dogs and continuous IV infusion of ceftazidime (loading dose, 4.4 mg/kg; infusion rate, 4.1 mg/kg/h) for 36 hours to 5 dogs. RESULTS: The MIC of ceftazidime for P aeruginosa was < or = 8 microg/ml; all isolates were considered susceptible. Following SC administration of ceftazidime, mean beta disappearance half-life was 0.8 hours, and mean serum ceftazidime concentration exceeded the MIC for P aeruginosa for only 4.3 hours. Two dogs had gastrointestinal tract effects. Mean serum ceftazidime concentration exceeded 16 microg/ml during continuous IV infusion. None of the dogs developed adverse effects. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of ceftazidime subcutaneously (30 mg/kg, q 4 h) or as a constant IV infusion (loading dose, 4.4 mg/kg; rate, 4.1 mg/kg/h) would maintain serum ceftazidime concentrations above the MIC determined for 101 clinical isolates of P aeruginosa. Use of these dosages may be appropriate for treatment of dogs with infections caused by P aeruginosa.     

Anaesthetic management for balloon dilation of cor triatriatum dexter in a dog

A three-month-old female Rottweiler puppy was referred for intravascular correction of a previously identified cor triatriatum dexter. Echocardiography confirmed the presence of a hyperechoic membrane that divided the right atrium into a cranial and caudal chamber. A foramen in this membrane allowed the blood to flow from the caudal to the cranial chamber. Balloon dilation of the defect under transthoracic echocardiographic guidance was scheduled for the following day. The dog was premedicated with 0.5 μg/kg sufentanil and 0.2 mg/kg midazolam administered intravenously. General anaesthesia was induced with 2 mg/kg propofol and maintained with inhaled isoflurane in oxygen; at the same time, a constant rate infusion of 0.5 μg/kg/h sufentanil was administered by means of an infusion pump. Uneventful ventricular and supraventricular tachyarrhythmias developed during the placement of catheters and balloon dilation. At the end of procedure, when the guide wire and balloon catheter were removed, normal sinus rhythm was observed. To the authors’ knowledge, no previous reports have described the anaesthetic management of a balloon dilation procedure for cor triatriatum dexter in dogs.     

The effects on maternal and fetal cardiovascular and acid-base variables after the administration of etomidate in the pregnant ewe

Etomidate is an intravenous (IV) hypnotic agent characterised by its cardiovascular stability. Although etomidate has been satisfactorily used in veterinary and human obstetrics, little is known about its effects on the fetus. This study determined the cardiovascular and acid-base effects of etomidate administration in the pregnant ewe and her fetus. The effects of etomidate were evaluated in two separate studies. In the first study, etomidate was administered as a 1mg/kg IV bolus; in the second, the drug was administered as a continuous infusion of 100 microg/kg/min for 1h, preceded by a 1mg/kg IV bolus. Etomidate administration did not depress cardiovascular function in the pregnant ewe or fetus. When administered as a continuous infusion, maternal heart rate and blood pressure increased during the second half of the infusion and the initial stages of recovery. Acid-base alterations led to transient but slight respiratory depression in both mother and fetus, probably reflecting the combined effects of etomidate on respiration and the positioning of the animal.     

Atracurium infusion in the dog

The non-depolarizing muscle relaxant atracurium was administered to 25 dogs undergoing a variety of surgical procedures under general anaesthesia. An initial dose of 0–5 mg/kg was administered and when the block began to wear off an infusion was begun. A dose of 0–5 mg/kg/hr was administered by a simple infusion technique. Reversal of the neuromuscular block was carried out with either neostigmine or edrophonium preceded by atropine.     

Naloxone reversal of oxymorphone effects in dogs

Oxymorphone was administered IV to dogs 4 times at 20-minute intervals (total dosage, 1 mg/kg of body weight, IV) on 2 separate occasions. Minute ventilation, mixed-expired carbon dioxide concentration, arterial and mixed-venous pH and blood gas tensions, arterial, central venous, pulmonary arterial, and pulmonary wedge pressures, and cardiac output were measured. Physiologic dead space, base deficit, oxygen transport, and vascular resistance were calculated before and at 5 minutes after the first dose of oxymorphone (0.4 mg/kg) and at 15 minutes after the first and the 3 subsequent doses of oxymorphone (0.2 mg/kg). During 1 of the 2 experiments in each dog, naloxone was administered 20 minutes after the last dose of oxymorphone; during the alternate experiment, naloxone was not administered. In 5 dogs, naloxone was administered IV in titrated dosages (0.005 mg/kg) at 1-minute intervals until the dogs were able to maintain sternal recumbency, and in the other 5 dogs, naloxone was administered IM as a single dose (0.04 mg/kg). Naloxone (0.01 mg/kg, IV or 0.04 mg/kg, IM) transiently reversed most of the effects of oxymorphone. Within 20 to 40 minutes after IV naloxone administration and within 40 to 70 minutes after IM naloxone administration, most variables returned to the approximate values measured before naloxone administration. The effects of oxymorphone outlasted the effects of naloxone; cardiovascular and pulmonary depression and sedation recurred in all dogs. Four hours and 20 minutes after the last dose of oxymorphone, alertness, responsiveness, and coordination improved in all dogs after IM administration of naloxone. Cardiac arrhythmia, hypertension, or excitement was not observed after naloxone administration.     

Evaluation of metoclopramide and ranitidine on the prevention of gastroesophageal reflux episodes in anesthetized dogs

This research aimed to evaluate the effect of metoclopramide and ranitidine in the prevention of gastroesophageal reflux episodes during anesthetic procedures. Ninety healthy female dogs were submitted to elective ovariosalpingohisterectomy, randomly divided into three groups of 30 animals. The control group received only the anesthetic protocol. The metoclopramide group received an intravenous bolus of 1mg/kg, and continuous infusion (1 mg/kg/h intravenously) immediately after anesthetic induction. The ranitidine group received an intravenous bolus of 2 mg/kg, 6 h before anesthesia. Anesthesia (acepromazine, propofol and isofluorane) was standardized and the esophageal pH variations were recorded. Esophagoscopy was carried out after surgery. No difference (p<0.05) was verified in the reflux episodes between the groups. Seven animals presented reflux. Metoclopramide in bolus and continuous infusion, as well as ranitidine, 6 h before anesthesia, did not influence the reduction of the incidence of gastroesophageal reflux.     

Sedative, analgesic, and cardiovascular effects of levomedetomidine alone and in combination with dexmedetomidine in dogs

OBJECTIVE: To determine whether a high dose of levomedetomidine had any pharmacologic activity or would antagonize the sedative and analgesic effects of dexmedetomidine in dogs. ANIMALS: 6 healthy Beagles. PROCEDURE: Each dog received the following treatments on separate days: a low dose of levomedetomidine (10 microg/kg), IV, as a bolus, followed by continuous infusion at a dose of 25 microg/kg/h; a high dose of levomedetomidine (80 microg/kg), IV, as a bolus, followed by continuous infusion at a dose of 200 microg/kg/h; and a dose of isotonic saline (0.9% NaCl) solution, IV, as a bolus, followed by continuous infusion (control). For all 3 treatments, the infusion was continued for 120 minutes. After 60 minutes, a single dose of dexmedetomidine (10 microg/kg) was administered IV. Sedation and analgesia were scored subjectively, and heart rate, blood pressure, respiratory rate, arterial blood gas partial pressures, and rectal temperatures were monitored. RESULTS: Administration of levomedetomidine did not cause any behavioral changes. However, administration of the higher dose of levomedetomidine enhanced the bradycardia and reduced the sedative and analgesic effects associated with administration of dexmedetomidine. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of dexmedetomidine alone may have some cardiovascular benefits over administration of medetomidine, which contains both dexmedetomidine and levomedetomidine. Further studies are needed to confirm the clinical importance of the effects of levomedetomidine in dogs.     

Evaluation of the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication

OBJECTIVE: To compare the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication. ANIMALS: 42 client-owned dogs that underwent elective ovariohysterectomy. PROCEDURE: Each dog was randomly allocated to receive medetomidine and butorphanol tartrate (20 microgram/kg and 0.2 mg/kg, respectively, IM) or acepromazine maleate and butorphanol (0.05 and 0.2 mg/kg, respectively, IM) for preanesthetic medication. Approximately 80 minutes later, anesthesia was induced by administration of propofol and maintained by use of isoflurane in oxygen. Each dog was also given carprofen before surgery and buprenorphine after surgery. Plasma concentrations of epinephrine, norepinephrine, cortisol, and beta-endorphin were measured at various stages during the perioperative period. In addition, cardiovascular and clinical variables were monitored. RESULTS: Concentrations of epinephrine, norepinephrine, and cortisol were significantly lower for dogs administered medetomidine. Concentrations of beta-endorphin did not differ between the 2 groups. Heart rate was significantly lower and mean arterial blood pressure significantly higher in dogs administered medetomidine, compared with values for dogs administered acepromazine. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that for preanesthetic medications, medetomidine may offer some advantages over acepromazine with respect to the ability to decrease perioperative concentrations of stress-related hormones. In particular, the ability to provide stable plasma catecholamine concentrations may help to attenuate perioperative activation of the sympathetic nervous system.     

Medetomidine/propofol anaesthesia for gastroduodenal endoscopy in dogs

This study was performed to evaluate clinically the level of analgesia obtained during fibre optic gastroduodenal examination with an anaesthetic regimen consisting of 1000 μg/m²b.s.a. medetomidine premedica-tion (equivalent to 30–50 μg/kg b.w, IM) followed by induction and maintenance of anaesthesia with propofol (1–2 mg/kg, IV), with spontaneous respiration of room air. Following premedication, all the dogs (n=20) were connected to an E.C.G. monitor (lead II) and a femoral artery catheter was placed for continuous recording of blood pressure and to allow sampling for arterial blood gas analysis. The mean values for heart rate and arterial blood pressure following medetomidine administration were 55 b.p.m. and 121 mm Hg, respectively, and these values remained unchanged during the procedure. Blood gas data all remained within physiological limits. Fibre optic gastroduodenoscopy could be performed without the occurrence of “pain” responses. In all but one dog, the pyloric sphincter was relaxed and it was easy to pass the endoscope into the duodenum. All the dogs recovered rapidly and smoothly from anaesthesia, following administration of atipamezole 2500 μg/m² b.s.a. (equivalent to 75–125 μg/kg b.w.) IM to reverse the effects of the medetomidine.     

Comparison of continuous infusion with intermittent bolus administration of cefotaxime on blood and cavity fluid drug concentrations in neonatal foals

Hewson, J., Johnson, R., Arroyo, L. G., Diaz‐Mendez, A., Ruiz‐López, J. A., Gu, Y., del Castillo, J. R. E. Comparison of continuous infusion with intermittent bolus administration of cefotaxime on blood and cavity fluid drug concentrations in neonatal foals. J. vet. Pharmacol. Therap.  36 , 68–77. Healthy neonatal foals were treated with cefotaxime by bolus (40 mg/kg IV q6h for 12 doses; n = 10) or by infusion (loading dose of 40 mg/kg IV followed by continuous infusion of a total daily dose of 160 mg/kg per 24 h for 3 days; n = 5). Population pharmacokinetics was determined, and concentrations in cavity fluids were measured at steady state (72 h). Highest measured serum drug concentration in the bolus group was 88.09 μg/mL and minimum drug concentration (C_min) was 0.78 μg/mL at 6‐h postadministration (immediately before each next dose), whereas infusion resulted in a steady‐state concentration of 16.10 μg/mL in the infusion group. Mean cefotaxime concentration in joint fluid at 72 h was higher (P = 0.051) in the infusion group (5.02 μg/mL) compared to the bolus group (0.78 μg/mL). Drug concentration in CSF at 72 h was not different between groups (P = 0.243) and was substantially lower than serum concentrations in either group. Insufficient data on pulmonary epithelial lining fluid were available to compare the methods of administration for cefotaxime in this cavity fluid. Results support continuous drug infusion over bolus dosing in the treatment for neonatal foal septicemia to optimize time that cefotaxime concentration exceeds the minimum inhibitory concentration of common equine pathogens.     

Pharmacokinetics of ticarcillin in the dog

Five healthy adult dogs were given a single IV dose (40 mg/kg of body weight) of ticarcillin disodium. Serum concentrations were measured serially over a period of 12 hours. Five days later, the drug was administered IM to the dogs at the same dose rate, and serum concentrations were measured serially for 12 hours. The mean peak serum concentration after IM administration was 120.5 micrograms/ml at 1.5 hours. Pharmacokinetic values following IV administration were (i) elimination rate constant = 0.8/hour-1, (ii) half-life = 0.8 hour, (iii) serum clearance = 292 ml/hr/kg, and (iv) apparent volume of distribution = 347 ml/kg. Estimated values after IM administration were (i) elimination rate constant = 0.6/hour, (ii) half-life = 1.1 hours, (iii) serum clearance = 218 ml/hr/kg, and (iv) apparent volume of distribution = 345 ml/kg; only the elimination rate constants were significantly different between the 2 routes of administration.