Effect of ingesta and of tablets of different strengths on the systemic availability of digoxin in normal dogs

The plasma concentrations of digoxin were measured in eight normal dogs given digoxin on four occasions, using three different feeding regimens and tablets of two strengths. Although ingesta tended to slow the absorption of digoxin, the systemic availability of the drug, based on measurements of C_max, t_max and Auc did not differ when digoxin tablets were given with canned food, with dry food, or without food. However, some of the pharmacokinetic characteristics and smaller individual variations with the dry food regimen would be considered advantageous for maintenance therapy. Tablets containing 62·5 μg or 250 μg of digoxin had a similar relative bioavailability. The peak plasma digoxin concentrations were higher in female dogs, and the trends in other data also suggested that the systemic availability of digoxin was better in female dogs.     

Plasma cortisol concentrations following cortisone infusion in dogs before and after treatment with cortisone acetate

OBJECTIVE: To evaluate effects of iatrogenic hyperadrenocorticism on plasma cortisol concentrations produced by an infusion of hydrocortisone in dogs. PROCEDURE: Plasma cortisol concentrations were measured regularly during a 6 h infusion of hydrocortisone sodium succinate at two dose rates. The infusions were performed before and after treatment for 30 d with oral cortisone acetate at 10 mg/kg/24 h, divided thrice daily. Adrenal activity during the experimental period was assessed by weekly ACTH stimulation tests. RESULTS: Both infusion rates produced lower plasma cortisol concentrations after treatment for 30 d with cortisone. CONCLUSION: Prior exposure to high concentrations of glucocorticoids may result in accelerated metabolism of glucocorticoids administered subsequently. This may necessitate increased dosages when using glucocorticoids to support inadequate adrenal function.     

Plasma cortisol responses to three cortico-trophic preparations in normal dogs

Objective To compare cortisol responses to three corticotrophic preparations in normal dogs.
Animals Eight clinically normal dogs (four intact males, four intact females) of medium size.
Procedures Each dog received four treatments on four separate occasions in a duplicated Latin square pattern. Treatments were two adrenocorticotrophin (ACTH) preparations given intramuscularly at 2.2 U/kg, one of the ACTH preparations given intramuscularly at 1 U/kg and a synthetic polypeptide with ACTH-like activity (tetracosactrin, cosyntropin) given intravenously at 5 μg/kg. Plasma samples were taken for cortisol assay before and at 0.5, 1, 2 and 4 h after treatment.
Results Plasma cortisol concentrations were similar with the two ACTH preparations and at both dose rates. Tetracosactrin produced smaller mean peak cortisol concentrations, which tended to occur earlier than with ACTH, and smaller values for the area under the curve of plasma cortisol concentration from zero time to 4 h.
Conclusion The findings suggest that canine adrenal function can be tested adequately by giving ACTH intramuscularly at 1 U/kg and measuring plasma cortisol in samples taken at 0 and 2 h, or by giving tetracosactrin intravenously at 5 μg/kg and determining cortisol concentration at 0 and 1 h.     

Serum concentrations of cortisol and cortisone in healthy dogs and dogs with pituitary-dependent hyperadrenocorticism treated with trilostane

The serum concentrations of cortisol and cortisone were measured in 19 healthy dogs and in 13 dogs with pituitary-dependent hyperadrenocorticism (PDH) before and one hour after an injection of synthetic adrenocorticotropic hormone (ACTH). In the dogs with pdh, the cortisol and cortisone concentrations were measured before and after one to two weeks and three to seven weeks of treatment with trilostane. The dogs with PDH had significantly higher baseline and poststimulation concentrations of cortisol and cortisone, and higher baseline cortisol:cortisone ratios than the healthy dogs. During the treatment with trilostane, the poststimulation cortisol, the baseline and poststimulation cortisone concentrations, and the baseline and poststimulation cortisol:cortisone ratios decreased significantly. The decrease in poststimulation cortisone was significantly smaller than the decrease in cortisol.     

Use of a low dose synthetic ACTH challenge test in normal and prednisone-treated dogs

The utility of a low dose (1 microgram/kg) synthetic ACTH challenge test in detecting moderate reductions in adrenocortical sensitivity in dogs was examined. First, the adrenocortical responses to an intravenous bolus of either 1 microgram/kg or 0.25 mg per dog of synthetic ACTH were compared in two groups of normal dogs. While plasma cortisol concentrations were similar in both groups 60 minutes after ACTH injection, dogs given 0.25 mg ACTH showed continued elevations in plasma cortisol concentrations at 90 and 120 minutes after ACTH injection. Later, the dogs previously tested with the 1 microgram/kg ACTH challenge were given a single intramuscular dose of prednisone (2.2 mg/kg) and retested with 1 microgram/kg of ACTH one week later. Plasma cortisol levels were significantly reduced after ACTH injection in dogs previously given prednisone demonstrating that a single intramuscular prednisone dose causes detectable adrenocortical suppression one week after administration. The 1 microgram/kg synthetic ACTH challenge test provides a sensitive means for evaluating adrenocortical suppression in dogs.     

Diagnosis of canine Cushing's syndrome based on multiple steroid analysis and dexamethasone turnover kinetics

A comparison of cortisol concentrations, determined by high-performance liquid chromatography (HPLC) and radioimmunoassay, was made in healthy, mixed-breed dogs and in dogs with clinical signs of Cushing's syndrome. Absolute concentration of cortisol was less in resting, dexamethasone-suppressed, and ACTH-stimulated plasma samples, when measured by HPLC relative to cortisol concentrations determined by radioimmunoassay. Diagnosis of Cushing's syndrome could be made using either method. Plasma concentrations of cortisone and corticosterone were determined by HPLC. Cortisone and corticosterone concentrations alone were not diagnostic of Cushing's syndrome; but when used in conjunction with cortisol determinations, they provided additional criteria for laboratory confirmation of the clinical diagnosis of Cushing's syndrome. The clearance of exogenous dexamethasone used in the dexamethasone-suppression test was examined in the normal and cushingoid dogs. Plasma concentrations of exogenous dexamethasone were constant during the 3-hour test in the normal dogs. However, in 75% of the dogs with Cushing's syndrome, exogenous dexamethasone was cleared completely in the 3-hour test. Thus, dexamethasone clearance rates were excessively fast in most dogs with Cushing's syndrome.     

Imepitoin as novel treatment option for canine idiopathic epilepsy: pharmacokinetics,distribution, and metabolism in dogs

Imepitoin is a novel anti‐epileptic licensed in the European Union for the treatment of canine idiopathic epilepsy. The aim of this study was to characterize the pharmacokinetics of imepitoin in dogs and to evaluate the interaction with drug metabolizing enzymes. Upon administration of imepitoin tablets at a dose of 30 mg/kg to beagle dogs, high plasma levels were observed within 30 min following oral dosing, with maximal plasma concentrations of 14.9–17.2 μg/mL reached after 2–3 h. In a crossover study, co‐administration of imepitoin tablets with food reduced the total AUC by 30%, but it did not result in significant changes in T_max and C_max, indicating lack of clinical relevance. No clinically relevant effects of sex and no accumulation or metabolic tolerance were observed upon twice daily dosing. Following single dose administration of 10–100 mg/kg, dose linearity was found. Administering [¹⁴C] imepitoin, high enteral absorption of 92% and primary fecal excretion were identified. Plasma protein binding was only 55%. At therapeutic plasma concentrations, imepitoin did not inhibit microsomal cytochrome P450 family liver enzymes in vitro. In rats, no relevant induction of liver enzymes was found. Therefore, protein binding or metabolism‐derived drug–drug interactions are unlikely. Based on these data, imepitoin can be dosed twice daily, but the timing of tablet administration in relation to feeding should be kept consistent.     

The effects of concurrent administration of cytochrome P-450 inhibitors on the pharmacokinetics of oral methadone in healthy dogs

ObjectiveThe objective was to examine the effects of inhibiting cytochrome P450 (CYP) on the pharmacokinetics of oral methadone in dogs.Study designProspective non-randomized experimental trial.AnimalsSix healthy Greyhounds (three male and three female).MethodsThe study was divided into two phases. Oral methadone (mean = 2.1 mg kg^?1 PO) was administered as whole tablets in Phase 1. In Phase 2 oral methadone (2.1 mg kg^?1 PO) was administered concurrently with ketoconazole (13.0 mg kg^?1 PO q 24 hours), chloramphenicol (48.7 mg kg^?1 PO q 12 hours), fluoxetine (1.3 mg kg^?1 PO q 24 hours), and trimethoprim (6.5 mg kg^?1 PO q 24 hours). Blood was obtained for analysis of methadone plasma concentrations by liquid chromatography with mass spectrometry. The maximum plasma concentration (C_max), time to C_max (T_max), and the area under the curve from time 0 to the last measurable time point above the limit of quantification of the analytical assay (AUC_0–LAST) were compared statistically.ResultsThe C_max of methadone was significantly different (p = 0.016) for Phase 1 (5.5 ng mL^?1) and Phase 2 (171.9 ng mL^?1). The AUC_0–LAST was also significantly different (p = 0.004) for Phase 1 (13.1 hour ng mL^?1) and Phase 2 (3075.2 hour ng mL^?1).Conclusion and clinical relevanceConcurrent administration of CYP inhibitors with methadone significantly increased the area under the curve and plasma concentrations of methadone after oral administration to dogs. Further studies are needed assessing more clinically relevant combinations of methadone and CYP inhibitors.     

Bioavailability of three brands of digoxin tablets in dogs

As information on the comparative bioavailability of digoxin tablets in dogs is scarce, three brands of digoxin tablets, commercially available in Belgium, were compared in 6 healthy dogs in a cross-over randomized design. Each dog received 1 mg digoxin on four occasions (once intravenously and 3 times orally). The mean areas under the curve relative to the intravenous value were 80, 71 and 65%. For the 3 oral preparations peak plasma concentrations were reached within 1 hour after dosing and often within 30 minutes. The mean peak concentrations were 11.0, 10.0 and 8.1 ng/ml. The times for 50% dissolution were 4.5, 7.5 and 25 minutes. Although differences between brands were only significant for the dissolution rate, the same ranking order was present for all parameters. It is therefore concluded that it may be advisable not to switch a digitalized dog from one brand to another.     

Restitution of blood volume after hemorrhage in dogs with adrenocortical suppression

Groups of splenectomized dogs were treated with weekly im doses of a potent glucocorticoid, methylprednisolone acetate (MPA; 2.5 mg/kg) or MPA-vehicle (controls) to determine if glucocorticoid-induced adrenocortical suppression would alter the restitution of blood volume in response to a 7.5 ml/kg hemorrhage. Five of the MPA-treated dogs were infused with cortisol (17 μg/min) for 2 hr beginning with the onset of hemorrhage. Blood volume restitution at 24 hr post-hemorrhage was reduced (P<0.05) in MPA-treated (46.5 ± 4.7%) or MPA-treated- cortisol infused (69.8 ± 9.7%) dogs as compared to controls (114 ± 11.8%). Hemorrhage was associated with a rapid increase in plasma immunoreactive (i) ACTH and cortisol concentrations in controls. In contrast, MPA treatment lowered baseline plasma iACTH and cortisol concentrations and prevented increases in either hormone following hemorrhage. Infusion of cortisol in one group of MPA-treated dogs gradually raised plasma cortisol concentrations but to lower (P<0.05) concentrations than measured in controls. Plasma aldosterone and glucose concentrations were not altered by MPA-treatment. Plasma osmolality increased to a greater (P<0.05) extent after hemorrhage in controls than in either group of MPA-treated dogs. It is concluded that glucocorticoid-induced adrenocortical suppression impairs the normal blood volume restitution process after moderate hemorrhage. The failure of cortisol infusion to fully restore restitution after MPA treatment may indicate that the pattern of the plasma cortisol response to hemorrhage is important in activating the restitution process or that MPA treatment diminishes non-cortisol dependent factors involved in restitution.     

Estimated plasma bupivacaine concentration after single dose and eight-hour continuous intra-articular infusion of bupivacaine in normal dogs

Objective— To estimate maximum plasma concentration (C_max) and time to maximum plasma (t_max) bupivacaine concentration after intra‐articular administration of bupivacaine for single injection (SI) and injection followed by continuous infusion (CI) in normal dogs. Study Design— Cross‐over design with a 2‐week washout period. Animals— Healthy Coon Hound dogs (n=8). Methods— Using gas chromatography/mass spectrometry, canine plasma bupivacaine concentration was measured before and after SI (1.5 mg/kg) and CI (1.5 mg/kg and 0.3 mg/kg/h). Software was used to establish plasma concentration–time curves and estimate C_max, T_max and other pharmacokinetic variables for comparison of SI and CI. Results— Bupivacaine plasma concentration after SI and CI best fit a 3 exponential model. For SI, mean maximum concentration (C_max, 1.33±0.954 μg/mL) occurred at 11.37±4.546 minutes. For CI, mean C_max (1.13±0.509 μg/mL) occurred at 10.37±4.109 minutes. The area under the concentration–time curve was smaller for SI (143.59±118.390 μg/mL × min) than for CI (626.502±423.653 μg/mL × min, P=.02) and half‐life was shorter for SI (61.33±77.706 minutes) than for CI (245.363±104.415 minutes, P=.01). The highest plasma bupivacaine concentration for any dog was 3.2 μg/mL for SI and 2.3 μg/mL for CI. Conclusion— Intra‐articular bupivacaine administration results in delayed absorption from the stifle into the systemic circulation with mean C_max below that considered toxic and no systemic drug accumulation. Clinical Relevance— Intra‐articular bupivacaine can be administered with small risk of reaching toxic plasma concentrations in dogs, though toxic concentrations may be approached. Caution should be exercised with multimodal bupivacaine administration because plasma drug concentration may rise higher than with single intra‐articular injection.     

Systemic availability of o,p'-DDD in normal dogs, fasted and fed, and in dogs with hyperadrenocorticism

The systemic availability of o,p'-DDD was studied in 12 normal dogs and seven dogs with pituitary-dependent hyperadrenocorticism (PDH). The drug was given by mouth at 50 mg kg-1 and plasma o,p'-DDD concentrations were determined by gas-liquid chromatography. First, six normal dogs were given the drug three times at intervals of one week in a Latin square pattern. Systemic drug availability was found to be very poor from intact tablets in fasted dogs, better with pure drug dissolved in maize oil given by stomach tube, and best with ground tablets mixed in oil poured on dog food. Then six normal dogs and five with PDH were given one dose of o,p'-DDD as intact tablets in dog food. Systemic drug availability was good in the normal animals and, for unknown reasons, better in dogs with PDH. The half-time of elimination was shorter in dogs with PDH than in normal ones. There was evidence of a gradual rise in plasma o,p'-DDD concentrations in seven dogs with PDH treated with 25 mg kg-1 every 12 hours for 14 or 20 days. The interaction between food and o,p'-DDD probably contributes to the variation in clinical response of dogs treated with the drug. The efficiency of therapy with o,p'-DDD should be improved considerably by administering the drug with food.     

Plasma free cortisol concentrations in dogs with hyperadrenocorticism.

Unbound or free cortisol constitutes a small fraction of total plasma cortisol, but is believed to represent the biologically active portion of this circulating glucocorticoid. We tested the hypothesis that the percentage free cortisol was altered in plasma from dogs with hyperadrenocorticism, which could account for a greater target tissue response to this circulating hormone. The percentage free cortisol in plasma samples from human beings, healthy dogs, and dogs with hyperadrenocorticism was estimated, using centrifugal ultrafiltration-dialysis. Total cortisol concentrations were determined by use of radioimmunoassay. Total cortisol concentrations appeared greater in plasma from human beings than in plasma from either group of dogs. However, the percentage free cortisol was lower in plasma from human beings, resulting in a calculated concentration of free cortisol that was quite similar between plasma from human beings and healthy dogs. Total plasma cortisol concentrations were greater (P less than 0.01) in samples from dogs with hyperadrenocorticism (190 +/- 113 nmol/L; mean +/- SD) than in healthy dogs (102 +/- 85 nmol/L), but the percentage free cortisol was not different between these 2 groups (dogs with hyperadrenocorticism, 16 +/- 9%; healthy dogs, 13 +/- 6%). However, plasma free cortisol concentrations (product of total and the percentage of free cortisol) were greater (P less than 0.01) in samples from dogs with hyperadrenocorticism (36 +/- 41 nmol/L) than in those from healthy dogs (16 +/- 9 nmol/L). Significant (P less than 0.001) positive linear relationships were found between total cortisol concentrations and percentage free cortisol in plasma samples from healthy dogs and dogs with hyperadrenocorticism.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of preoperative tramadol and morphine for the control of early postoperative pain in canine ovariohysterectomy

Objective To compare morphine with tramadol for the management of early postoperative pain following ovariohysterectomy after pyometra in dogs. Study design Prospective randomized blinded clinical trial. Animals Thirty female dogs, 2–14 years old. Methods Animals were randomly divided into two equal groups. Group 1 received 0.2 mg kg^?1 of morphine IV and group 2 received 2 mg kg^?1 of tramadol IV after the induction of anesthesia. The dogs were premedicated with acepromazine, and anesthesia was induced with intravenous midazolam and ketamine. Isoflurane was used for the maintenance of anesthesia. The variables measured were: analgesia; sedation; cardiac and respiratory rates; arterial blood pressure; end‐tidal isoflurane and carbon dioxide (Pe ′CO₂); oxyhemoglobin saturation (SpO₂); plasma catecholamines; serum cortisol and glucose concentrations; pH and blood gases. The animals were monitored for 6 hours after the administration of the analgesic agent. Results There were no differences between the two groups with regard to analgesia, sedation, SpO₂, pH and blood gases, cardiovascular variables, glucose, catecholamine and cortisol concentrations. Forty minutes postopioid administration, the end‐tidal isoflurane concentration was significantly lower in the morphine‐treated group as compared to the tramadol group. At 30 minutes following opioid injection, Pe ′CO₂ was significantly higher in the morphine group than in the tramadol group. Two dogs in the tramadol group and one in the morphine group were given morphine postoperatively because of increasing pain scores. Conclusion and clinical relevance Morphine and tramadol, administered preemptively can be used safely in dogs to control early pain after ovariohysterectomy without significant adverse effects.     

Pharmacokinetics of erythromycin after the administration of intravenous and various oral dosage forms to dogs

The purpose of this study was to describe and compare the pharmacokinetic properties of different formulations of erythromycin in dogs. Erythromycin was administered as lactobionate (10 mg/kg, IV), estolate tablets (25 mg/kg p.o.) and ethylsuccinate tablets or suspension (20 mg/kg p.o.). After intravenous (i.v.) administration, the principal pharmacokinetic parameters were (mean ± SD): AUC_(0–∞) 4.20 ± 1.66 μg·h/mL; C_max 6.64 ± 1.38 μg/mL; V_z 4.80 ± 0.91 L/kg; Cl_t 2.64 ± 0.84 L/h·kg; t_½λ 1.35 ± 0.40 h and MRT 1.50 ± 0.47 h. After the administration of estolate tablets and ethylsuccinate suspension, the principal pharmacokinetic parameters were (mean ± SD): C_max, 0.30 ± 0.17 and 0.17 ± 0.09 μg/mL; t_max, 1.75 ± 0.76 and 0.69 ± 0.30 h; t_½λ, 2.92 ± 0.79 and 1.53 ± 1.28 h and MRT, 5.10 ± 1.12 and 2.56 ± 1.77 h, respectively. The administration of erythromycin ethylsuccinate tablets did not produce measurable serum concentrations. Only the i.v. administration rendered serum concentrations above MIC₉₀ = 0.5 μg/mL for 2 h. However, these results should be cautiously interpreted as tissue erythromycin concentrations have not been measured in this study and, it is recognized that they can reach much higher concentrations than in blood, correlating better with clinical efficacy.     

Interspecies variations of corticosteroid-binding globulin parameters

In mammalian plasma, cortisol binds to a specific α₁-glycoprotein: corticosteroid-binding globulin (CBG). In this study, we measured the protein binding of cortisol by equilibrium dialysis in seven species in which plasma cortisol concentrations varied from 0.02 to 0.05 (ewe, dog, cow) to 0.1 to 0.6 (horse, human, cynomolgus monkey) to reach 1.6 μM (squirrel monkey). No binding of cortisol to CBG was discernible in plasma from squirrel monkey. In all other species examined, we showed that the CBG maximal capacity (B_max) was 3 (1.7 to 5.2) times more than the plasma cortisol levels, with cow, dog, ewe exhibiting the lowest and cynomolgus monkey exhibiting the highest values. We also noted the existence of a linear relationship between B_max and the corresponding dissociation constant (K_d), B_max being systematically 10 (8.5 to 11.8) times more than K_d. The low binding affinity of cortisol assigned to albumin did not differ between species. The free (6 to 14%), CBG-bound (67 to 87%), and albumin-bound (7 to 19%) cortisol fractions calculated from the estimated binding parameters and measured plasma cortisol concentrations were similar within species, except for squirrel monkey, in which half of the cortisol was albumin bound, and the other half remained protein free. Our most appealing finding was that in most species, as much as 68% of plasma CBG remained free of cortisol under physiologic conditions. These results are discussed with respect to the theories concerning the role of CBG in plasma transport and the local delivery of cortisol and free CBG as a proper hormone.     

Plasma cortisol response to exogenous ACTH in 22 dogs with hyperadrenocorticism caused by adrenocortical neoplasia

The plasma cortisol response to exogenous ACTH (ACTH stimulation test) was evaluated in 22 dogs with hyperadrenocorticism caused by adrenocortical neoplasia. The mean basal cortisol concentration (6.3 microgram/dl) was high, but 7 dogs had basal cortisol concentrations that were within normal range. Administration of exogenous ACTH increased the plasma cortisol concentrations in each dog. Normal post-ACTH cortisol concentrations were found in 9 (41%) of the 22 dogs; 13 (59%) had an exaggerated increase in cortisol concentrations after ACTH administration. In 9 of 13 dogs with carcinoma and in 4 of 9 with adenoma, the cortisol response was exaggerated. The mean post-ACTH cortisol concentration in the dogs with carcinoma was approximately 4 times that of the dogs with adenoma; the 7 dogs with the highest concentrations had carcinoma. Repeat studies were performed in 6 dogs 2 to 8 weeks after initial testing. In 5 of the 6 dogs, repeat testing yielded data of similar diagnostic significance. One dog, however, had an abnormally high post-ACTH cortisol concentration at initial evaluation, but had only a minimal response to ACTH administration, with a normal post-ACTH cortisol concentration, at time of resting. Although ACTH stimulation testing is useful in diagnosing hyperadrenocorticism, it can not reliably separate dogs with hyperfunction adrenocortical tumors from clinically normal dogs or from dogs with pituitary-dependent hyperadrenocorticism (bilateral adrenocortical hyperplasia).     

Simultaneous steroids measurement in dogs with hyperadrenocorticism using a column-switching liquid chromatography-tandem mass spectrometry method

We developed an analytical method using an on-line column-switching liquid chromatography with triple quadrupole mass spectrometry (LC/MS/MS) for quantifying multiple steroids in serum. Using the developed method, we evaluated the serum concentration of nine steroids (cortisol, corticosterone, cortisone, 11-deoxycortisol, 21-deoxycortisol, deoxycorticosterone, progesterone, 17α-OH-progesterone and aldosterone) in dogs with hyperadrenocorticism (HAC). Serum was mixed with stable isotope internal standards and thereafter purified by the automated column-switching system. The limit of detection ranged 2–16 pg/ml for nine steroids. In the baseline samples, five steroids (cortisol, corticosterone, cortisone, 11-deoxycortisol, and 17α-OH-progesterone) were detected in all dogs. The concentrations of cortisone, 11-deoxycortisol, and 17α-OH-progesterone in dogs with HAC (n=19) were significantly higher those in dogs without HAC (n=15, P<0.02). After the adrenocorticotropic hormone stimulation test, six steroids (cortisol, corticosterone, cortisone, 11-deoxycortisol, 17α-OH-progesterone, and deoxycorticosterone) were above the limit of quantification in all dogs. Cortisol, corticosterone, cortisone, and deoxycorticosterone concentrations of dogs with HAC were significantly higher than those of dogs without HAC (P<0.02). In addition, 11-deoxycortisol and 17α-OH-progesterone concentration was higher in dogs with HAC than in dogs without HAC (P=0.044 and P=0.048, respectively). The on-line column-switching LC/MS/MS would be feasible for measuring multiple steroids in dog serum. The results suggest that cortisone, 11-deoxycortisol, and 17α-OH-progesterone would be related to HAC. Further studies are warranted to assess the clinical feasibility of steroid profile in dogs with HAC.     

Plasma cortisol concentrations in normal dogs given hydrocortisone sodium succinate

OBJECTIVE: To evaluate the effects on plasma cortisol concentration of a continuous infusion of a readily available steroid with equipotent glucocorticoid and mineralocorticoid effects. PROCEDURE: Plasma cortisol concentrations were measured before and regularly after hydrocortisone sodium succinate was administered as a continuous intravenous infusion over 6 h at 0.32 and 0.65 mg kg-1 h-1 to 12 healthy dogs weighing 12 to 22 kg. RESULTS: The infusion at both does rates produced significant and stable increases in plasma cortisol concentrations. The plateau concentrations produced by the large and small doeses were respectively above and below plasma cortisol concentrations likely to provide adequate glucocorticoid and mineralocorticoid activity in stressed dogs with significantly decreased adrenal function. CONCLUSION: This paper presents information regarding the changes in plasma cortisol concentrations in 12 normal dogs given an hydrocortisone sodium succinate infusion at two dose rates. The marked and continuous increase in plasma cortisol concentrations suggests a continuous HSS infusion may be a possible alternative to desoxycorticosterone acetate and dexamethasone in the treatment of acute adrenal dysfunction.     

Catecholamine and cortisol responses of horses to incremental exertion

The responses of the plasma concentrations of catecholamines and cortisol in horses to varied relative intensities of exertion were examined. The plasma concentrations of cortisol, epinephrine and norepinephrine increased significantly (p<0.05) with exertion. The plasma cortisol concentrations at relative work intensities of 48.3%±1.4%, 82.3%±2.0% and 99.6%±0.4% of VO_2max were 114%, 124%, and 126%, respectively, of those at rest, whereas the plasma epinephrine concentrations were 239%, 772% and 3483%, and the norepinephrine concentrations were 138%, 255%, and 1121% of the values at rest. There was a significant (p<0.0001) relationship between the plasma epinephrine and norepinephrine concentrations. The blood lactate concentration and the plasma epinephrine and norepinephrine concentrations were significantly (p<0.0001) related, as were the relative work intensity (%VO_2max) and the plasma epinephrine and norepinephrine concentrations. The relationships between the plasma cortisol concentration and work intensity or blood lactate concentration were not significant (p>0.05). This study demonstrates a relationship between relative work intensity and indicators of adrenal medullary and sympathetic activity during brief exertion in horses.