Pharmacokinetics of tobramycin in the camel

A/Hadi, A.A., Wasfi, I.A., Gadir, F.A., Amiri, M.H., Bashir, A.K. Baggot, J.D. Pharmacokinetics of tobramycin in the camel. J. vet. Pharmacol. Therap. 17 . 48–51.
The pharmacokinetics of tobramycin were determined in six healthy camels (Camelus dromedarius) following the intravenous (i.v.) and intramuscular (i.m. administration of single doses of tobramycin sulphate (40 mg/ml). The half-life to tobramycin was 189 ± 21 min and the mean residence time was 254 ± 26 min. The apparent volume of distribution (area method) was 245 ± 21 ml/kg. while volume of the central compartment of the two-compartment pharmaco-kinetic model was 110 ± 12 ml/kg. The clearance (systemic) of tobramycin was 0.90 ± 0.10 ml/min/kg. Values of the pharmacokinetic parameters suggest that glomerular filtration rate is lower in camels than in other ruminant species, horses, dogs and cats. Following i.m. administration of the dose (1.0 mg/kg), the drug was rapidly absorbed with peak serum concentration of 3.32 ± o.59 g/ml at 20–30 min; the absorption half-life was 3.9 ± 0.9 min. The systemic availability of tobramycin was 90.7 ± 14.4%. The apparent half-life was 201 ±40 min, which was not significantly longer than the half-life following i.v. administration of the drug. Based on the pharmacokinetic values obtained in this study, a dosing rate of 2.5 mg/kg administered by i.m. injection at 12-h intervals can be recommended. This dosage regimen should achieve an average steady state serum concentration of 4 g/ml with peak serum concentration approaching, but not exceeding, 10 g/ml.     

Thiopentone pharmacokinetics and electrocorticogram pattern in sheep

Thiopentone pharmacokinetics and electrocorticogram patterns were studied in a group of six sheep given thiopentone intravenously (20 mg/kg). Plasma concentrations were determined using a high-performance liquid chromatography method. A three-compartment open model was selected to describe the disposition kinetics of thiopentone. The drug had an apparent volume of distribution of 1005 ± 196 ml/kg; body clearance was 3.5 ± 0.8 ml/minkg and the half-life, based on the slope of the terminal portion of the curve, was 196 ± 64 min. From the electrocorticogram pattern, it seems likely that the highest concentrations in brain occurred between 47 and 217 sec after commencing administration and a brain penetration half-time of 26.5 ± 2.87 sec was calculated. At the time of awakening (36.6 ± 6.36 min) 24.1 ± 6.3% of the dose was located in the central compartment, 12.6 ± 8.2 was in the shallow peripheral compartment, 38.8 ± 14.1 was in the deep peripheral compartment and 24.6 ± 10.3 had been eliminated. Using simulated curves, it appeared that suppression of the shallow peripheral compartment (muscle) did not change the time of awakening; in contrast when elimination-rate constant was decreased, awakening was delayed. It was suggested that the relatively short duration of thiopentone anaesthesia in sheep should be attributed mainly to elimination of the drug by hepatic metabolism and uptake by body fat. This hypothesis, which differs from the widely accepted view that the duration of thiopentone anaesthesia is independent of the rate of hepatic metabolism, is discussed in terms of differences in regional blood flow between sheep and monogastric species.     

The pharmacokinetics and locomotor activity of alfentanil in the horse

The pharmacokinetics of alfentanil were investigated in the horse. Four doses of alfentanil (4, 10, 20 and 40 micrograms/kg) were given to four horses at different times and their locomotor activity monitored. Doses of 20 and 40 micrograms/kg produced a significant increase in locomotor activity. The plasma concentrations of alfentanil were measured in six standing horses and the pharmacokinetics calculated. It was found that the decay curves were best described by a biexponential equation. The elimination half-life (t1/2 beta) was 21.65 +/- 3.99 min and the clearance (Cl) was 14.1 +/- 0.7 ml/kg/min. The same horses were anaesthetized with xylazine-ketamine and maintained with halothane in oxygen for the first experiment and isoflurane in oxygen for the second experiment. The pharmacokinetics were again calculated from measured plasma alfentanil concentrations. There were significant differences between the kinetics in the conscious and the anaesthetized animals but there were no significant differences in alfentanil kinetics between the two anaesthetic agents. The t1/2 beta for alfentanil under halothane and isoflurane anaesthesia were 55.95 +/- 20.77 and 68.03 +/- 23.22 min, respectively, and the Cl values were 14 +/- 1.7 and 13.6 +/- 1.32 ml/kg/min.     

The pharmacokinetics of thiopentone

The pharmacokinetics of thiopentone was studied in six mongrel dogs using a high-performance liquid chromatographic method for measurement of the drug in the plasma. An intravenous bolus dose (20 mg/kg) of 2.5% thiopentone sodium solution was injected into the cephalic vein. While the two- and three-compartment models were used in the analysis of the experimental data, the disposition curve was adequately described by a biexponential equation. Plasma protein binding of thiopentone was determined in vitro using the equilibrium dialysis technique. The drug was bound to a moderately high extent (73.8 ± 4.1%). The half-time of the initial phase, which comprises distribution/redistribution, was 14.9 ± 3.3 mins. The apparent volume of distribution was quite high for an organic acid (843 ± 194 ml/kg). This may be attributed to the high lipid solubility of the thiobarbiturate. The half-life was 6.99 ± 2.18 h and a body clearance value of 1.51 ± 0.60 ml/kg-min was obtained. It can be concluded from this study that the half-time of the distribution/redistribution phase approximates the duration of anaesthetic effect. Consequently, physiological conditions and disease states which influence distribution/redistribution rather than those affecting hepatic biotransformation of the drug are likely to affect anaesthesia.     

Pharmacokinetics of chloramphenicol in the neonatal horse

Chloramphenicol sodium succinate was administered as an intravenous bolus (50 mg/kg) to eight foals which weighed 49–57 kg (mean ± 1 standard deviation = 53.19 ± 2.66) each, and were 1–9 days (4.5 ± 2.56) of age. The drug was rapidly distributed and followed first-order elimination. Mean pharmacokinetic values were: zero-time serum concentration (C₀) = 36.14 μg/ml (±14.80); apparent specific volume of distribution ( V_d ) = 1.614 1/kg (±0.669); and elimination rate constant ( K ) = 0.7295 h^-1 (±0.3066) which corresponds to a biological half-life ( t _1/2) = 0.95 h. These values do not differ greatly from those reported for adult horses and ponies.
A suspension of chloramphenicol was administered by nasogastric tube (50 mg/kg) to a second group of seven foals which weighed 49 to 57 kg (51.34 ± 2.82) each and were 1 to 7 days (4.43 ± 1.90) of age. A mean peak serum chloramphenicol concentration of 23.97 μg/ml (±7.06) was achieved 1.14h (±0.63) after administration. The bioavailability of this preparation was 83.27 percent.     

Plasma disposition of amikacin and interactions with gastrointestinal microflora in Equidae following intravenous and oral administration

Amikacin was detectable (> 0.02 μg/ml) in plasma for 12 h in horses and donkeys and for 8 h in ponies following intravenous (i.v.) administration at a dose the rate of 6 mg/kg bodyweight The elimination half-life (harmonic mean) of amikacin was 2.8, 1.6 and 1.9 h in horses, ponies and donkeys, respectively, and the mean body clearance was relatively slow (45.2, 82.4 and 58.0 ml/h.kg, respectively). A suitable dosage interval for the i.v. administration of amikacin sulphate to horses, ponies and donkeys, at a dose rate of 6 mg/kg, would be every 8 h in horses, and every 6 h in ponies and donkeys. Following i.v. administration there were no marked alterations in caecal liquor pH, the number of viable bacteria isolated, or the short chain fatty acid (SCFA) concentrations in caecal liquor and faeces. Amikacin was not detected (< 0.02 μg/ml) in plasma following administration by nasogastric tube to ponies with cannu-lated caecal fistulae; however, there were high concentrations of amikacin measured in caecal liquor (maximum 16.2–99.4 μg/ml). Despite the high drug concentrations in caecal liquor, there were only slight alterations in the number of viable bacteria isolated. However, there was a reduction in caecal liquor pH to < 6.6, but few changes in caecal liquor SCFA concentrations. Faecal SCFA concentrations, dry matter content and consistency did not alter markedly.     

Midazolam and ketamine induction before halothane anaesthesia in ponies: cardiorespiratory, endocrine and metabolic changes

Six Welsh gelding ponies were premedicated with 0.03 mg/kg of acepromazine intravenously (i.v.) prior to induction of anaesthesia with midazolam at 0.2 mg/kg and ketamine at 2 mg/kg i.v.. Anaesthesia was maintained for 2 h using 1.2 % halothane concentration in oxygen. Heart rate, electrocardiograph (ECG), arterial blood pressure, respiratory rate, blood gases, temperature, haematocrit, plasma arginine vasopressin (AVP), dynorphin, ß-endorphin, adrenocorticotropic hormone (ACTH), cortisol, dopamine, noradrenaline, adrenaline, glucose and lactate concentrations were measured before and after premedication, immediately after induction, every 20 min during anaesthesia, and at 20 and 120 min after disconnection. Induction was rapid, excitement-free and good muscle relaxation was observed. There were no changes in heart and respiratory rates. Decrease in temperature, hyperoxia and respiratory acidosis developed during anaes-thesia and slight hypotension was observed (minimum value 76 ± 10 mm Hg at 40 mins). No changes were observed in dynorphin, ß-endorphin, ACTH, catecholamines and glucose. Plasma cortisol concentration increased from 220 ± 17 basal to 354 ± 22 nmol/L at 120 min during anaesthesia; plasma AVP concentration increased from 3 ± 1 basal to 346 ± 64 pmol/L at 100 min during anaesthesia and plasma lactate concentration increased from 1.22 ± 0.08 basal to 1.76 ± 0.13 mmol/L at 80 min during anaesthesia. Recovery was rapid and uneventful with ponies taking 46 ± 6 min to stand. When midazolam/ketamine was compared with thiopentone or detomidine/ketamine for induction before halothane anaesthesia using an otherwise similar protocol in the same ponies, it caused slightly more respiratory depression, but less hypotension. Additionally, midazolam reduced the hormonal stress response commonly observed during halothane anaesthesia and appears to have a good potential for use in horses.     

The pharmacokinetics of ketamine after a continuous infusion under halothane anaesthesia in horses

The pharmacodynamics and pharmacokinetics of ketamine, when administered by infusion as an adjunct to halothane anaesthesia in horses, were investigated in 5 equine patients presented for routine castration. Anaesthesia was induced with detomidine, 20 μg/kg, followed by ketamine, 2.2 mg/kg bwt, the trachea intubated and the horses allowed to breathe halothane in oxygen. Five minutes later, a constant rate infusion of ketamine, 40 μg/kg min, was commenced and the halothane vaporiser concentration adjusted to maintain a light plane of anaesthesia. The mean infusion duration was 62 min (range 40–103). The ketamine was switched off approximately 15 min before the halothane. Plasma ketamine and norketamine levels, determined by high performance liquid chromatography, ranged from 0.74–2.04 μg/ml and 0.15–0.75 μg/ml, respectively, during the infusion period. The harmonic mean elimination half-life of ketamine was 46.1 min, mean volume of distribution at steady state (Vdss) was 1365 (271) ml/kg, mean body clearance (Cl) was 32.3 (9.1) ml/min.kg, and average mean residence time for the infusion (MRTinf) was 105.9 (20.4) min, respectively. Following termination of halothane, mean times to sternal recumbency and standing were 21.1 (6.9) and 41.6 (17.0) min, respectively. Surgical conditions were considered highly satisfactory, and physiological parameters were well preserved in most animals.     

Pharmacokinetics of phenolsulfonphthalein in horse and pony mares

Pharmacokinetics of phenolsulfonphthalein (PSP) in horse and pony mares was determined after injection of 1 mg/kg of body weight, IV. A plasma PSP concentration vs time curve was described adequately in horses and ponies by an open, 2-compartment model. There were significant differences in the elimination phase parameters, apparent volume of distribution at steady state, and apparent volume of distribution of horses and ponies. The harmonic mean elimination half-life of PSP in horses was significantly longer (P less than 0.001) than that in the ponies (16.4 and 10.0 minutes, respectively). The mean plasma clearance of PSP in horses was significantly (P less than 0.05) less than that in ponies (0.00554 and 0.00701 L/min/kg, respectively). There was no difference between horses and ponies in the metabolic clearance of PSP. The fraction of the administered dose of PSP excreted in the urine in the first 15 minutes was not significantly different between horses and ponies.     

Does the induction agent affect the course of halothane anaesthesia in horses?

Four hundred and ninety horses were anaesthetised with halothane for clinical surgical or diagnostic procedures following induction with either detomidine/keta-mine, detomidine/thiopentone, xylazine/ketamine or guaiphenesin/thiopentone. Routine clinical monitoring was performed during anaesthesia. All horses developed hypotension (mean arterial pressures below 80 mm Hg) and respiratory depression (significant fall in respiratory rate and arterial carbon dioxide tension above 7 kPa (53 mm Hg)) consistent with the recognised effects of halothane. All anaesthetic procedures incorporating xylazine or detomidine resulted in lower pulse rates (28–35 per min) than after guaiphenesin/thiopentone (36–44 per min) and there was greater respiratory depression after techniques employing thiopentone rather than keta-mine. Development of hypotension was delayed after techniques using the α₂ adrenoceptor agonist agents (xylazine and detomidine), particularly detomidine. Prernedication with acepromazine did not affect any of the physiological variables measured after techniques employing detomidine. Recovery to standing was fastest after xylazine/ketamine (31±1 min) and slowest after detomidine/thiopentone (53±2 min). Recovery quality was best after detomidine/thiopentone and all techniques employing an α₂ adrenoceptor agonist agent resulted in smoother recovery than after guaiphenesin/thiopentone. This study demonstrates that most of the physiological effects of individual induction agents are overridden by the cardiovascular and respiratory depressant effects of halothane. The study also shows that detomidine is an acceptable sedative for use before general anaesthesia with halothane in horses.     

Pharmacokinetics of ciprofloxacin in ponies

The pharmacokinetics of ciprofloxacin was investigated in healthy, mature ponies. Ciprofloxacin was administered intravenously to six ponies at a dose of 5 mg per kg body weight. Seven days later, ciprofloxacin was administered orally to each pony at the same dose. Intravenous ciprofloxacin concentration vs. time data best fit a two-compartment open model with first-order elimination from the central compartment. Mean plasma half-life, based on the terminal phase, was 15 7.8 9 min (harmonic mean). Total body clearance of ciprofloxacin was 18.12 ± 3.99 mL/min/kg. Volume of distribution at steady-state was 3.45 ± 0.72 L/kg. From the pharmacokinetic data and reported minimum inhibitory concentrations for equine gram-negative pathogens, the appropriate dosage of ciprofloxacin was determined to be 5.32 mg per kg body weight at 12 h intervals. Bioavailability of oral ciprofloxacin in ponies was 6.8 ± 5.33%. Owing to the poor bioavailability, a dosage regimen could not be proposed for oral ciprofloxacin administration in horses. Ciprofloxacin concentrations were determined in tissues and body fluids at 1, 2 and 4 h after intravenous administration. At all times, tissue concentrations exceeded plasma concentrations of ciprofloxacin. Highest concentrations were achieved in kidneys and urine. Potentially therapeutic concentrations were obtained in cerebrospinal and joint fluid, but low concentrations were achieved in aqueous humour.     

Pharmacokinetic, biochemical and tolerance studies on carprofen in the horse

Carprofen, a non-steroidal anti-inflammatory drug (NSAID) was administered to three Thoroughbred geldings and three Shetland ponies to determine its plasma disposition and tolerance. The main pharmacokinetic characteristics of carprofen in horses and ponies were a volume of distribution of 0.08 to 0.32 litres/kg (mean +/- se = 0.23 +/- 0.04) a systemic clearance of 26.4 to 78.5 ml/min (mean +/- se = 44.9 +/- 8.0) and a plasma elimination half-life of 14.5 to 31.4 h (mean +/- se = 21.9 +/- 2.3). There was no evidence of any accumulation of carprofen in plasma when the drug was given orally at a dose rate of 0.7 mg/kg for 14 consecutive days. Carprofen was well tolerated following intravenous (iv) and oral administration. Intramuscular (im) administration resulted in elevated levels of plasma creatine kinase suggesting muscle cell damage. According to the results of this study carprofen can be regarded as a long-acting NSAID in horses from a pharmacokinetic point of view. Either iv, im or the oral route of administration could be used to achieve high carprofen plasma concentrations.     

Electroencephalography of Detomidine-Ketamine-Halothane and Detomidine-Ketamine-lsoflurane Anesthetized Horses During Orthopedic Surgery A Comparison

This study was done to compare the electroencephalographic (EEG) response evoked by orthopedic surgery in halothane- and isoflurane-anesthetized horses. Eight horses scheduled for bilateral arthroscopic surgery of the stifle were premedicated with detomidine (20 μg/kg) intravenously and five minutes later induced to anesthesia with ketamine (2.2 mg/kg) intravenously. Anesthesia was maintained with either halothane or isoflurane. Assignment of inhalation anesthetic was done randomly. The multiple of minimal alveolar concentration (MAC) of halothane required for anesthesia was significantly higher than the multiple of MAC of isoflurane (p < .05) required. Total amplitude of the EEG with halothane was smaller than with isoflurane (p < .05), but 13.0 to 32.0 Hz high frequency/0.0 to 3.9 Hz low frequency (|3/A) ratio was greater for halothane (p < .05). Arterial partial pressure of oxygen (PaO₂) was significantly (p < .05) higher with isoflurane than with halothane. The differences in EEG frequency shift observed suggest that isoflurane provided better analgesia than halothane for this group of horses.     

Endocrine and metabolic responses to plasma volume expansion during halothane anaesthesia in ponies

The study was designed to contribute to identification of the stimulus to adrenocortical activity during halothane anaesthesia in equidae . Two groups of six ponies were premedicated with acepromazine before induction of anaesthesia with thiopentone and maintenance for 120 min with halothane in oxygen. In group H Haemaccel® modified gelatine plasma replacer was infused (48 ± 13 mL/kg) to maintain mean arterial blood pressure (MABP) close to preanaesthetic values. In group DH, blood pressure was maintained close to preanaesthetic levels with a lower dose of Haemaccel® (10 mL/kg) combined with an infusion of dobutamine. Measurements were made before anaesthesia, at 20 min intervals during anaesthesia and 20 and 120 min after anaesthesia. MABP and blood gases, pulse and respiratory rates were measured, and blood was withdrawn for assay of cortisol, adrenocorticotrophic hormone (ACTH), glucose and lactate. Ponies in both groups became hyperoxic, hypercapnic and developed a respiratory acidosis; pulse rate increased in both groups but this was more marked in group H. Haematocrit decreased by 50% in H and by 20% in DH. Cortisol and ACTH did not change significantly during anaesthesia in either group and the area under the time curve ( AUC _(0–140)) was lower in the DH group. Plasma glucose and lactate remained stable. After the H treatment all ponies had a watery nasal discharge and one pony died from endotoxaemia. This investigation demonstrated that the adrenocortical response to halothane anaesthesia in ponies can be ameliorated by manipulation of ABP using plasma expansion with or without inotrope infusion; however, low dose Haemaccel® with dobutamine was safer and more practical. It is suggested that, although hypotension is not the sole stimulus to adrenocortical activity during halothane anaesthesia, it may contribute, probably through an effect on tissue perfusion.     

Hemodynamic effects of ionized calcium in horses anesthetized with halothane or isoflurane

OBJECTIVES: To evaluate the effects of halothane and isoflurane on cardiovascular function and serum total and ionized calcium concentrations in horses, and to determine whether administration of calcium gluconate would attenuate these effects. ANIMALS: 6 clinically normal adult Thoroughbreds. PROCEDURE: Catheters were inserted for measurement of arterial blood pressures, pulmonary arterial blood pressures, right ventricular pressure (for determination of myocardial contractility), right atrial pressure, and cardiac output and for collection of arterial blood samples. Anesthesia was then induced with xylazine hydrochloride and ketamine hydrochloride and maintained with halothane or isoflurane. An i.v. infusion of calcium gluconate was begun 75 minutes after anesthetic induction; dosage of calcium gluconate was 0.1 mg/kg of body weight/min for the first 15 minutes, 0.2 mg/kg/min for the next 15 minutes, and 0.4 mg/kg/min for an additional 15 minutes. Data were collected before, during, and after administration of calcium gluconate. RESULTS: Halothane and isoflurane decreased myocardial contractility, cardiac index, and mean arterial pressure, but halothane caused greater depression than isoflurane. Calcium gluconate attenuated the anesthetic-induced depression in cardiac index, stroke index, and maximal rate of increase in right ventricular pressure when horses were anesthetized with isoflurane. When horses were anesthetized with halothane, a higher dosage of calcium gluconate was required to attenuate the depression in stroke index and maximal rate of increase in right ventricular pressure; cardiac index was not changed with calcium administration. CONCLUSIONS AND CLINICAL RELEVANCE: I.v. administration of calcium gluconate may support myocardial function in horses anesthetized with isoflurane.     

Use of guaiacol glycerine ether in clinical anaesthesia in the horse

A total of 103 anaesthetic inductions were performed in horses for a variety of elective procedures. All cases were premedicated with acepromazine maleate (0.02 to 0.05 mg/kg body weight [bwt] intramuscularly [im]). In 50 cases (Group A) anaesthesia was induced by a single intravenous (iv) bolus of thiopentone sodium (11.1 mg/kg bwt or 1 g/90 kg bwt) followed immediately by a bolus of suxamethonium chloride (0.1 mg/kg bwt). In 53 cases (Group B) anaesthesia was induced using iv guaiacol glycerine ether (GGE) (approximately 50 mg/kg bwt) followed by a bolus of thiopentone at half the usual dose rate (5.6 mg/kg bwt or 1 g/180 kg bwt). Induction of anaesthesia was uneventful in both groups although in Group B it was particularly smooth. Following endotracheal intubation anaesthesia was maintained with halothane in oxygen administered via a circle system. The duration of anaesthesia was comparable between the two groups; however, the mean (+/- sd) time to standing in Group B, 35 +/- 22 mins, was significantly shorter than in Group A, 48 +/- 25 mins. The use of the GGE/thiopentone technique is discussed.     

Dose-sparing effects of romifidine premedication for thiopentone and halothane anaesthesia in the dog

Two intravenous doses of romifldine (40 and 80 μg/kg) and a placebo were compared as premedicants for anaesthesia induced with thiopentone and maintained using halothane in oxygen. Romifldine significantly and linearly reduced the induction dose of thiopentone; placebo-treated dogs required 15.1 ± 3.6 mg/kg, while dogs treated with 40 μg/kg and 80 μg/kg romifldine required 6.5 ± 1.6 and 3.9 ± 0.3 mg/kg thiopentone, respectively.
Romlfldine also significantly and linearly reduced the end tidal halothane concentration necessary to maintain a predetermined level of anaesthesia; piacebetreated dogs required 1.6 ± 0.3 per cent halothane, while dogs treated with 40 μg/kg and 80 μg/kg romifldine required 1.3 ± 0.4 and 0–8 ± 0.2 per cent, respectively.
Romifldine produced a significant shortening In the recovery from anaesthesia, and the higher dose of romlfldine significantly improved the overall quality of anaesthesia.     

Pharmacokinetics of dantrolene sodium in horses

The pharmacokinetics of dantrolene sodium were investigated in horses following both intravenous (2 mg/kg) and intragastric (4 mg/kg) administration. Two ponies also received dantrolene sodium intravenously (2 mg/kg) in a pilot study to obtain preliminary kinetic data and to determine urinary and biliary excretion of the intact drug. Distribution and elimination of dantrolene was rapid, resulting in an elimination half-life of 129 +/- 8 (SEM) min and a whole body clearance of 4.16 +/- 0.52 ml/min/kg. Following intragastric administration, dantrolene rapidly acheived peak concentrations within 1.5 h, but was incompletely absorbed, with a bioavailability of 39 +/- 10%. Small amounts of intact drug were recovered in urine and bile. Based upon disposition kinetics of dantrolene in these studies, intravenous and intragastric dosage regimens were determined which would maintain blood dantrolene concentrations within the predicted clinically effective range.     

Adrenocortical and metabolic responses to dobutamine infusion during halothane anaesthesia in ponies

The study investigated whether hypotension in halothane-anaesthetised ponies is the stimulus inducing an endocrine stress response by assessing the effect of maintenance of normotension with a dobutamine infusion. Groups of six ponies were studied. After premedication with acepromazine (0.04 mg/kg) anaesthesia was induced with thiopentone (10 mg/kg) and maintained for 120 min with halothane (group AN). Dobutamine was infused to effect (1.1–4.4 μg/kg/min) to maintain arterial pressure at pre anaesthetic levels. The conscious group (CON) were prepared as for AN and then received only dobutamine infusion 1.0 μg/kg/min for 120 min. Arterial blood pressure, pH, oxygen and carbon dioxide tension, pulse rate, haematocrit, and plasma cortisol, glucose and lactate concentrations were measured before, at 20 min intervals during anaesthesia, and 20 and 120 min after anaesthesia ceased. Blood pressure remained close to control in both groups. The AN group became hypercapnic and acidotic, pulse rate and haematocrit increased, cortisol increased more than twofold and plasma glucose and lactate did not change. All values remained at control in the CON group except for small increases in haematocrit and decreases in pulse rate. Maintenance of normotension during halothane anaesthesia did not blunt the adrenocortical response to anaesthesia nor did the same dose of dobutamine alone increase plasma cortisol. Hypotension appears not to be the sole stimulus to equine adrenocortical activity during halothane anaesthesia.     

Metocurine pharmacokinetics and pharmacodynamics in goats

Non-depolarizing muscle relaxants can facilitate surgery and anaesthesia in numerous species, and volatile inhalational anaesthetics such as isoflurane potentiate their action. We studied the effect of isoflurane on the pharmacodynamics and pharmacokinetics of metocurine in six goats. Each was studied twice: once during barbiturate-opiate anaesthesia and once during isoflurane anaesthesia. The evoked response to sciatic nerve stimulation was measured using a force transducer attached to the hoof. Metocurine was infused until approximately 80–90% blockade. Plasma metocurine concentration was determined by high-performance liquid chromatography. Isoflurane increased the potency of metocurine significantly; IC₅₀ (the concentration in the effect compartment at 50% paralysis) was 70 ± 15 ng/mL during isoflurane anaesthesia and 129 ± 42 ng/mL during barbiturate-opiate anaesthesia ( P < 0.03). Volume of distribution (63 ± 18 mL/kg), clearance (1.6 ± 0.4 mL/min±kg) and elimination half-life (99 ± 9 min) during barbiturate-opiate anaesthesia were not significantly different during isoflurane anaesthesia: 64 ± 25 mL/kg, 1.5 ± 0.7 mL/kgmin, 116 ± 16 min respectively. We conclude that, relative to barbiturate-opiate anaesthesia, isoflurane potentiates metocurine in goats.