Pharmacokinetics of single doses of phenobarbital given intravenously and orally to dogs

Pharmacokinetics of phenobarbital was studied in 10 healthy dogs after single IV or oral administration. Phenobarbital sodium was administered IV to 5 dogs in group A (5.5 mg/kg of body weight) and 5 dogs in group B (15 mg/kg). Serial venous blood samples (n = 21) were collected from each dog before (base line) and after the administration of phenobarbital sodium for pharmacokinetic evaluation. After a 30-day resting period, 3 dogs in group A and 3 in group B were randomly selected and used for an IV crossover treatment. The IV treatment mean half-life of phenobarbital sodium was 92.6 +/- 23.7 and 72.3 +/- 15.5 hours, whereas mean total clearance was 5.60 +/- 2.31 and 6.66 +/- 0.78 ml/hr/kg for doses of 5 and 15 mg/kg, respectively. The mean residence time was 124 +/- 34 hours and 106 +/- 23 hours for the 5.5 and 15 mg/kg, IV doses, respectively. Significant differences (P greater than 0.05) were not observed in pharmacokinetic parameters between the 2-dose study. After a 35-day resting period, dogs in groups A and B were treated as described for the single IV treatment, except that they were given a phenobarbital tablet orally. Serial venous blood samples (n = 24) were collected before (base line) and after the administration of phenobarbital. Mean bioavailability was 88.1 +/- 12.4% and 96.8 +/- 9.0%, half life of absorption was 0.263 +/- 0.185 and 0.353 +/- 0.443 hour, and lag time was 0.611 +/- 0.683 and 0.741 +/- 0.554 hour for groups A and B, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adrenal response to adrenocorticotropic hormone in dogs before and after surgical attenuation of a single congenital portosystemic shunt

BACKGROUND: Dogs with single congenital portosystemic shunts (CPSS) often develop postoperative hypoglycemia and prolonged anesthetic recovery. These abnormalities could be attributable to inadequate adrenal response. However, adequacy of adrenal response after CPSS surgery is unexplored. HYPOTHESIS: Dogs with CPSS have inadequate postoperative adrenal response. ANIMALS: Eight nonoperated, 8 ovariohysterectomy (OHE), and 16 CPSS dogs. METHODS: Consecutive day ACTH stimulation tests were performed on nonoperated healthy dogs, healthy dogs before and after OHE, and CPSS dogs before and after surgery. Adequate response was defined as >50% or >30 ng/mL increase in cortisol after ACTH administration. Blood glucose (BG) was monitored before and after surgery. Prolonged anesthetic recovery and refractory hypoglycemia episodes were recorded. RESULTS: Results of consecutive day ACTH stimulation tests did not vary in normal dogs. Results of preoperative ACTH stimulation tests of CPSS and OHE dogs were not significantly different. Dogs with CPSS had higher postoperative baseline cortisol concentrations (median, 329 ng/mL) than OHE dogs (median, 153 ng/mL). Postoperative cortisol increase after ACTH in CPSS was < or =50% in 10/16 and < or =30 ng/mL in 6/16. After surgery, BG was < or =60 mg/dL in 7/16 CPSS dogs. Cortisol concentrations were not correlated with BG. Two CPSS dogs had refractory hypoglycemia and 4 had delayed recovery; all improved with dexamethasone administration (0.1-0.2 mg/kg/IV). CONCLUSIONS AND CLINICAL IMPORTANCE: Contrary to previous reports, baseline cortisol concentrations in CPSS and healthy dogs are similar. Many CPSS dogs have postoperative hypercortisolemia. Response to ACTH does not correlate with postoperative hypoglycemia or prolonged anesthetic recovery.     

Evaluation of a low-dose synthetic adrenocorticotropic hormone stimulation test in clinically normal dogs and dogs with naturally developing hyperadrenocorticism.

OBJECTIVE: To determine whether low doses of synthetic ACTH could induce a maximal cortisol response in clinically normal dogs and to compare a low-dose ACTH stimulation protocol to a standard high-dose ACTH stimulation protocol in dogs with hyperadrenocorticism. DESIGN: Cohort study. ANIMALS: 6 clinically normal dogs and 7 dogs with hyperadrenocorticism. PROCEDURE: Each clinically normal dog was given 1 of 3 doses of cosyntropin (1, 5, or 10 micrograms/kg [0.45, 2.3, or 4.5 micrograms/lb] of body weight, i.v.) in random order at 2-week intervals. Samples for determination of plasma cortisol and ACTH concentrations were obtained before and 30, 60, 90, and 120 minutes after ACTH administration. Each dog with hyperadrenocorticism was given 2 doses of cosyntropin (5 micrograms/kg or 250 micrograms/dog) in random order at 2-week intervals. In these dogs, samples for determination of plasma cortisol concentrations were obtained before and 60 minutes after ACTH administration. RESULTS: In the clinically normal dogs, peak cortisol concentration and area under the plasma cortisol response curve did not differ significantly among the 3 doses. However, mean plasma cortisol concentration in dogs given 1 microgram/kg peaked at 60 minutes, whereas dogs given doses of 5 or 10 micrograms/kg had peak cortisol values at 90 minutes. In dogs with hyperadrenocorticism, significant differences were not detected between cortisol concentrations after administration of the low or high dose of cosyntropin. CLINICAL IMPLICATIONS: Administration of cosyntropin at a rate of 5 micrograms/kg resulted in maximal stimulation of the adrenal cortex in clinically normal dogs and dogs with hyperadrenocorticism.     

Pharmacokinetics of single doses of digoxin administered intravenously to ducks, roosters, and turkeys

A single dose of digoxin was injected, IV, into 5 mature male turkeys (0.066 mg/kg of body weight), 8 male ducks (0.066 mg/kg), and 6 roosters (0.33 mg/kg). Twenty-three serial venous blood samples were collected before (baseline) and after the administration of digoxin to turkeys, ducks, and roosters. Plasma concentrations of digoxin were determined in duplicate by a radioimmunoassay that was validated for avian species. The plasma concentrations were best fitted by a 3 (turkeys, ducks)- and 2 (roosters)-compartment open model, with first-order elimination from the central compartment. Significant (P less than 0.05) kinetic differences were determined among species. Mean half-life (t1/2) for ducks, roosters, and turkeys were 8.30 +/- 2.70 (mean +/- SD), 6.67 +/- 3.50, and 23.7 +/- 4.8 hours, respectively. The volume of distribution at steady state (Vss) was 14.7 +/- 2.9, 3.13 +/- 0.49, and 2.27 +/- 0.36 L/kg, and total body clearance (CL) of drug was 1.54 +/- 0.43, 0.461 +/- 0.187, and 0.136 +/- 0.022 L/h/kg for ducks, roosters, and turkeys, respectively. The mean residence time was 10.3 +/- 3.9, 8.37 +/- 4.97, and 16.8 +/- 2.2 hours, respectively. Volume of distribution at steady state and CL in ducks were several fold higher than that in turkeys. The terminal half-life of digoxin determined for ducks and roosters in this study was considerably shorter than those previously reported for several mammalian species.     

Stages of hyperadrenocorticism: response of hyperadrenocorticoid dogs to the combined dexamethasone suppression/ACTH stimulation test

A study was designed to evaluate the response of blood cortisol content in dogs tentatively diagnosed as having hyperadrenocorticism by using the combined dexamethasone suppression/ACTH stimulation test procedure. Four groups of abnormal responses were identified in 54 dogs. In group I (14.8% of the dogs with abnormal responses), the only abnormality was partial suppression with dexamethasone (clinically normal dogs suppressed to less than 10 ng/ml). In group II (29.6%), 2 abnormalities were found: partial suppression with dexamethasone and hyperreactivity to the ACTH stimulation test. In group III (typical pituitary-dependent hypercortisolism, 48.1%), 3 abnormalities were found: base-line hypercortisolemia, partial suppression with dexamethasone, and hyperreactivity to the ACTH stimulation test. In group IV (7.4%), 2 abnormalities were found: base-line hypercortisolemia and partial suppression with dexamethasone. Base-line blood cortisol content was normal in 44.4% of the adrenopathic dogs. A normal response to ACTH stimulation was seen in 25.9% of the dogs, and 74.1% of the dogs hyperreacted to the ACTH stimulation test. All of the adrenopathic dogs were found to suppress partially with dexamethasone. Failure to suppress the adrenal gland completely (less than 10 ng/ml) with dexamethasone was the most consistent finding in adrenopathic dogs when using the combined dexamethasone suppression/ACTH stimulation test procedure. It was concluded that the test procedure is feasible, flexible, and convenient for clinical situations. Also, these results suggested that there may be several stages in the negative feedback failure associated with hyperadrenocorticism in dogs.     

Effects of single intravenous doses of dexamethasone on baseline plasma cortisol concentrations and responses to synthetic ACTH in healthy dogs

The duration of adrenocortical suppression resulting from a single IV dose of dexamethasone or dexamethasone sodium phosphate was determined in dogs. At 0800 hours, 5 groups of dogs (n = 4/group) were treated with 0.01 or 0.1 mg of either agent/kg of body weight or saline solution (controls). Plasma cortisol concentrations were significantly (P less than 0.01) depressed in dogs given either dose of dexamethasone or dexamethasone sodium phosphate by posttreatment hour (PTH) 2 and concentrations remained suppressed for at least 16 hours. However, by PTH 24, plasma cortisol concentrations in all dogs, except those given 0.1 mg of dexamethasone/kg, returned to control values. Adrenocortical suppression was evident in dogs given 0.1 mg of dexamethasone/kg for up to 32 hours. The effect of dexamethasone pretreatment on the adrenocortical response to ACTH was studied in the same dogs 2 weeks later. Two groups of dogs (n = 10/group) were tested with 1 microgram of synthetic ACTH/kg given at 1000 hours or 1400 hours. One week later, half of the dogs in each group were given 0.01 mg of dexamethasone/kg at 0600 hours, whereas the remaining dogs were given 0.1 mg of dexamethasone/kg. The ACTH response test was then repeated so that the interval between dexamethasone treatment and ACTH injection was 4 hours (ACTH given at 1000 hours) or 8 hours (ACTH given at 1400 hours). Base-line plasma cortisol concentrations were reduced in all dogs given dexamethasone 4 or 8 hours previously.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of age on the pharmacokinetics of single dose ceftiofur sodium administered intramuscularly or intravenously to cattle

The effects of maturation on the intravenous (IV) and intramuscular (IM) pharmacokinetics of ceftiofur sodium following a dose of 2.2 mg ceftiofur equivalents/kg body weight were evaluated in 16 one-day-old Holstein bull calves (33-53 kg body weight initially; Group 1) and 14 six-month-old Holstein steers (217-276 kg body weight initially; Group 2). Group 1 calves were fed unmedicated milk replacer until 30 days of age and were then converted to the same roughage/concentrate diet as Group 2. Groups 1-IV and 2-IV received ceftiofur sodium IV, and Groups 1-IM and 2-IM received ceftiofur sodium IM. Group 1 calves were dosed at 7 days of age and at 1 and 3 months of age; group 2 calves were dosed at 6 and 9 months of age. Blood samples were obtained serially from each calf, and plasma samples were analysed using an HPLC assay that converts ceftiofur and all desfuroylceftiofur metabolites to desfuroylceftiofur acetamide. C_max values were similar in all calves, and were no higher in younger calves than in older calves. Plasma concentrations remained above 0.150 μg ceftiofur free acid equivalents/mL for 72 h in 7-day-old calves, but were less than 0.150 μg/mL within 48 h following IV or IM injection for 6- and 9-month-old calves. Intramuscular bioavailability, assessed by comparing the model-derived area under the curve (AUC_mod) from IM and IV injection at each age, appeared to be complete. After IV administration, the AUC_mod in 7-day-old and 1-month-old calves (126.92±21.1 μg-h/mL and 135.0±21.6 μg.h/mL, respectively) was significantly larger than in 3-, 6- and 9-month-old calves (74.0±10.7 μg.h/mL, 61.0±17.7 μg.h/mL and 68.5±12.8 μg.h/mL, respectively; P< 0.0001). The V_d(ss) decreased linearly within the first 3 months of life in cattle (0.345±0.0616 L/kg, 0.335±0.919 L/kg and 0.284±0.0490 L/kg, respectively; P= 0.031), indicative of the decreasing extracellular fluid volume in maturing cattle. The Cl_b was significantly smaller in 7-day-old and 1-month-old calves (0.0178±0.00325 L/h.kg and 0.0167±0.00310 L/h.kg, respectively) than in 3-, 6- and 9-month-old calves (0.0303±0.0046 L/h.kg, 0.0398±0.0149 L/h.kg and 0.0330±0.00552 L/h.kg, respectively; P≦0.001). This observation may be indicative of maturation of the metabolism and/or excretion processes for ceftiofur and desfuroylceftiofur metabolites. The approved dosage regimens for ceftiofur sodium of 1.1-2.2 mg/kg administered once daily for up to 5 consecutive days will provide plasma concentrations above the MIC for bovine respiratory disease pathogens for a longer period of time in neonatal calves than in older calves. Peak plasma concentrations of ceftiofur and desfuroylceftiofur metabolites were no higher in neonatal calves than in more mature cattle, highly suggestive that peak tissue concentrations would be no higher in neonatal calves than in more mature cattle.     

Single- and multiple-dose pharmacokinetics of intravenously administered vancomycin in dogs

Vancomycin was administered IV to healthy adult female dogs at a dosage of 15 mg/kg of body weight every 12 hours for 10 days. Pharmacokinetic values were determined after the first and last doses. The disposition of vancomycin was not altered by multiple dosing, and little accumulation attributable to multiple dosing was observed. Serum vancomycin concentration after the first and last dose were described, using a 2-compartment open model with first-order elimination. The distribution and elimination half-lives after the single dose were 15.4 +/- 2.7 minutes and 137 +/- 21.8 minutes (geometric mean +/- pseudo-SD), respectively; whereas the distribution and elimination half-lives after the last dose were 11.3 +/- 2.61 minutes and 104 +/- 11.2 minutes, respectively. The mean (+/- SD) area-derived volume of distribution was 396 +/- 156 ml/kg and 382 +/- 160 ml/kg after the first and last dose, respectively. Serum vancomycin clearance was 2.13 +/- 0.35 ml/min/kg and 2.49 +/- 0.79 ml/min/kg after the first and last dose, respectively, and 25 to 49% of the total dose of vancomycin was recovered in the urine in the first 24 hours after the single dose administered IV. Mean serum vancomycin concentration reached 101.8 +/- 30.6 micrograms/ml and 99.7 +/- 28.0 micrograms/ml at 5 minutes after a single dose and the last of the multiple doses, respectively, and decreased to 0.94 +/- 0.58 microgram/ml and 1.51 +/- 1.44 micrograms/ml, respectively, at 12 hours after administration. The side effects that accompany vancomycin treatment in human beings were not observed in the dogs; all remained healthy through the end of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adrenal cortex response to adrenocorticotropic hormone in dairy cattle

Adult dairy cows were treated with a range of doses (0.0125mg to 0.4mg) of synthetic ACTH_1–24 and the plasma cortisol response was measured. Peak response was independent of dose. Higher doses of ACTH had a more prolonged effect such that the integrated response was dose dependent. Dose response curves were examined by regression analyses. Individual cows had a significant effect on y-axis intercept but not on the slope of the regression lines examined. A dose rate of 0.05mg ACTH iv was identified as a suitable dose rate for use in clinical assessment of adrenal cortex function, with 0, 50 and 120 min following ACTH being critical sampling times to identify the response.     

Pharmacokinetics of clindamycin HCl administered intravenously, intramuscularly and subcutaneously to dogs

A buffered aqueous solution of clindamycin Hcl (200 mg/mL) was injected intravenously (i.v.) intramuscularly (i.m.) and subcutaneously (s.c.) in a non-randomized, partial cross-over trial involving six male and six female dogs. Blood samples were collected at conventional, predetermined time periods and serum drug concentrations were determined by microbiological assay. Dogs were observed clinically for signs of pain, and activity of serum creatine phosphokinase (CPK) was monitored after i.m. dosing. The i.v. data from five of the dogs best fitted a two-compartment open-system pharmacokinetic model whereas a non-compartment model was most suitable for analysis of the data from the remaining seven dogs. The mean i.v. elimination half-life (t1/2 beta) and the mean residence time (MRT) were 124 and 143 min, respectively. The mean volume of distribution at steady state (Vss) was 0.86 L/kg. Little pain was recorded upon i.m. injection; mean peak serum drug concentration (Cmax) was 4.4 micrograms/mL, the elimination half-life (t1/2el) was 247 min and the calculated bioavailability (F) was 115% of the i.v. dose. Serum CPK activity was elevated to 25-fold the pretreatment level in samples collected 4, 8 and 12 h after i.m. injection. Pain was not recorded after s.c. drug administration; the mean Cmax of 20.8 micrograms/mL was significantly greater than the corresponding value for the i.m. route, and F was 310%. The s.c. route appears to be superior to the i.m. route in terms of local tolerance and serum drug level; a 10 mg/kg SID treatment regimen is suggested for treatment of canine infections due to clindamycin sensitive bacteria.     

Plasma and urine pharmacokinetics of intravenously administered flunixin in greyhound dogs

Medication control in greyhound racing requires information from administration studies that measure drug levels in the urine as well as plasma, with time points that extend into the terminal phase of excretion. To characterize the plasma and the urinary pharmacokinetics of flunixin and enable regulatory advice for greyhound racing in respect of both medication and residue control limits, flunixin meglumine was administered intravenously on one occasion to six different greyhounds at the label dose of 1 mg/kg and the levels of flunixin were measured in plasma for up to 96 hr and in urine for up to 120 hr. Using the standard methodology for medication control, the irrelevant plasma concentration was determined as 1 ng/ml and the irrelevant urine concentration was determined as 30 ng/ml. This information can be used by regulators to determine a screening limit, detection time and a residue limit. The greyhounds with the highest average urine pH had far greater flunixin exposure compared with the greyhounds that had the lowest. This is entirely consistent with the extent of ionization predicted by the Henderson–Hasselbalch equation. This variability in the urine pharmacokinetics reduces with time, and at 72 hr postadministration, in the terminal phase, the variability in urine and plasma flunixin concentrations are similar and should not affect medication control.     

Pharmacokinetics of pethidine administered intramuscularly and intravenously to dogs over 10 years old

The pharmacokinetics of pethidine administered postoperatively both intravenously and intramuscularly was investigated in dogs aged over 10 years. When the drug was given intravenously (2 mg kg-1), plasma levels declined in a biexponential manner, with an elimination half-life of 62.7 minutes. Following its intramuscular administration at the same dose rate, absorption was very slow and two distinct rates of absorption were observed. Maximum plasma concentrations were not achieved until 33 minutes after drug administration. The elimination of the intramuscularly administered drug was also slow with a t 1/2 beta' of 145.9 minutes. Thus, it seems that in elderly animals pethidine has a long elimination half-life and a slowed rate of absorption. However, the total body clearance of the drug does not seem to be affected by age.     

Evaluation of a combined dexamethasone suppression/ACTH stimulation test in dogs with hyperadrenocorticism

Twenty-one dogs with hyperadrenocorticism were studied. Six dogs had functioning adrenocortical tumors and 15 had pituitary-dependent hyperadrenocorticism. Each dog was evaluated, using endogenous plasma ACTH, ACTH stimulation, dexamethasone screening, dexamethasone suppression, and combined dexamethasone suppression/ACTH stimulation tests. The ACTH stimulation portion of the combined test was less reliable as a screening test in diagnosing hyperadrenocorticism than was the isolated ACTH stimulation test or the dexamethasone screening test. The dexamethasone suppression portion of the combined test was less reliable in distinguishing dogs with adrenocortical tumors from those with pituitary-dependent hyperadrenocorticism than was the endogenous ACTH or isolated dexamethasone suppression test. The combined test is not recommended for use. The ACTH stimulation test is the recommended screening test because of its diagnostic reliability and its subsequent importance as a base line in determining success of mitotane therapy.     

Pharmacokinetics of single doses of gentamicin given intravenously and intramuscularly to turkeys

The disposition and absorption kinetics of gentamicin were studied in healthy, mature male and female turkeys (n = 10). Single doses of gentamicin (5 mg/kg) were injected either i.v. or i.m. with a 30-day rest period between each treatment. Baseline and serial venous blood samples (n = 17) were collected from each turkey. Serum concentrations of gentamicin were determined in duplicate for 24 h after each treatment, using radio-immunoassay. Using nonlinear least-square regression methods, the combined data of the i.v. and i.m. treatments were best described by a two-compartment open model. Kinetic analysis of the data after a single i.v. dose provided the following mean values: t1/2 alpha = 0.170 +/- 0.093 h, t1/2 beta = 2.57 +/- 0.79 h, MRT = 3.62 +/- 0.96 h, Vc = 0.090 +/- 0.017 l/kg, Vd(ss) = 0.172 +/- 0.024 l/kg, Vd(area) = 0.190 +/- 0.030 l/kg, and Clt = 49.8 +/- 9.8 ml/h/kg. After a single i.m. dose, the following mean values were determined: MRT = 5.10 +/- 1.73 h, t1/2abs = 0.74 +/- 0.66 h, tlag = 0.07 +/- 0.19 h, Clt/F = 50.7 +/- 12.5 ml/h/kg, Vd(area)/F = 0.193 +/- 0.044 l/kg, and F = 102 +/- 21%. Kinetic calculations made with the single i.m. data predicted that an i.m. injection of gentamicin at the dosage rate of 3 mg/kg q. every 12 h would provide average steady state serum concentrations of 4.93 micrograms/ml.     

Pharmacokinetics and bioavailability of 2-mercaptopropionylglycine administered intravenously and orally in dogs

The pharmacokinetic disposition of 2-mercaptopropionylglycine (2-MPG) given as a single intravenous injection and/or as a single oral dose was studied in 9 normal and 13 cystinuric dogs. After intravenous injection of approximately 10 or 20 mg/kg body weight the pharmacokinetics were best described by a three-exponential function. The first phase involved a distribution process apparently including establishment of drug-plasma protein and drug-tissue binding. The second phase involved rapid renal elimination and 60% of the drug was excreted within 3 h of administration. There was also a slow terminal third phase with a long half-life after both intravenous (t1/2 = 23 h) and oral (t1/2 = 22 h) administration. No dose dependency was observed. A deep pool of reversibly tissue-bound 2-MPG was indicated by a Vss of 3.3 +/- 0.9 l/kg body weight and the long terminal elimination phase. Total clearance was estimated as 4.1 +/- 0.9 ml/min/kg body weight. 2-MPG was eliminated mainly by renal excretion, but there was a difference in recovery of dose between normal and cystinuric dogs. During the first 24 h after intravenous and oral administration, 69% and 54%, respectively, of the drug was recovered in the urine of normal dogs. The corresponding figures in cystinuric dogs were 44% and 29%, respectively. The absolute bioavailability (FAUC) was 88 +/- 20% in normal dogs.     

Effects of intravenously administered glycopyrrolate in anesthetized horses.

The purpose of this study was to determine the heart rate (HR) and blood pressure (BP) effect of glycopyrrolate in anesthetized horses with low HR (< or = 30 beats/min). The horses were randomly treated with glycopyrrolate (2.5 micrograms/kg body weight (BW)) or saline, intravenously (i.v.) (n = 17). If HR failed to increase (by > 5 beats/min within 10 min), glycopyrrolate (same dose) was administered. Heart rate increased by > 5 beats/min in 3 out of 9 horses following the initial glycopyrrolate treatment. Overall changes in HR and mean BP were not significantly different, while systolic and diastolic BP increased significantly (P < 0.025 using a Bonferroni corrected paired t-test). On the 2nd treatment, 3 out of 7 horses given 2.5 micrograms/kg BW glycopyrrolate, and 4 out of 5 horses given 5.0 micrograms/kg BW (total dose) showed an increase in heart rate of > 5 beats/min, which was significant. A significant increase in BP was produced following treatment with 2.5 micrograms/kg BW, but not following 5.0 micrograms/kg BW. A final increase in HR, of > 5 beats/min, was associated with a significant rise in BP (P < 0.05 using an unpaired t-test). In conclusion, an increase in HR can occur with 2.5 to 5.0 micrograms of glycopyrrolate/kg BW, i.v., and results in improvement in BP in anesthetized horses.     

Evaluation of a six-hour combined dexamethasone suppression/ACTH stimulation test in dogs with hyperadrenocorticism

Seventeen dogs with hyperadrenocorticism were studied. Three dogs had functioning adrenocortical tumors and 14 had pituitary-dependent hyperadrenocorticism. Each dog was evaluated by determining the endogenous plasma ACTH concentration and by performing 4 tests: ACTH stimulation, dexamethasone screening, dexamethasone suppression, and a 6-hour combined dexamethasone suppression/ACTH stimulation test. The combined test was less reliable as a screening test in diagnosing hyperadrenocorticism than was the dexamethasone screening test or the ACTH stimulation test. Compared with the endogenous plasma ACTH concentration, results of the dexamethasone suppression portion of the combined test were less reliable in distinguishing dogs with adrenocortical tumors from those with pituitary-dependent hyperadrenocorticism. It was concluded that the combined test cannot be recommended for use.     

Plasma cortisol and progesterone responses to low doses of adrenocorticotropic hormone in ovariectmized lactating cows

The objective of this study was to describe the responses of the plasma progesterone and cortisol concentrations in ovariectomized lactating cows to low doses of adrenocorticotropic hormone (ACTH). The estrous cycles in 3 lactating cows were synchronized, and the cows were ovariectomized in the luteal phase. ACTH challenge tests were conducted at doses of 3, 6, 12 and 25 IU. Blood samples were collected at 30 min intervals, and the plasma progesterone and cortisol concentrations were analyzed by EIA. A concomitant rise in plasma progesterone and plasma cortisol was observed in cows treated with 12 IU or higher doses of ACTH. Significant increments in the plasma cortisol concentrations were observed at all doses of ACTH. The means (+/- SE) of the peak plasma progesterone concentrations after the 3, 6, 12 and 25 IU ACTH challenge tests were 0.6 +/- 0.1, 1.3 +/- 0.4, 1.5 +/- 0.3 and 2.4 +/- 0.3 ng/ml, respectively. The means of the peak plasma cortisol concentrations in the 3 cows after the ACTH challenge were 14.0 +/- 1.5, 17.0 +/- 2.5, 23.3 +/- 3.0, and 33.3 +/- 7.0 ng/ml, respectively. The effects of the doses, time after treatment, and their interaction on the plasma progesterone concentrations after the ACTH challenge were significant (P<0.01). Likewise, the effects of the doses, time after treatment, and their interaction on the plasma cortisol concentrations after the ACTH challenge were significant (P<0.01). The mean AUC values for the plasma progesterone and cortisol concentrations after the ACTH treatments were also significantly affected by the dose of ACTH (P<0.01 and P<0.05, respectively). A significantly positive correlation was obtained between the peak plasma progesterone and cortisol concentrations after different doses of ACTH (r=0.7, P<0.05). The results suggest that lactating dairy cows are capable of secreting a significant amount of adrenal progesterone, reaching up to the minimal concentration necessary to cause suppression of estrus in response to 12 IU ACTH (P<0.01). The concomitant plasma cortisol concentration was 23.3 ng/ml.     

Use of recombinant human thyroid-stimulating hormone for thyrotropin stimulation test in euthyroid dogs

The purpose of this study was to evaluate the effects of the recombinant human thyroid-stimulating hormone (rhTSH) on serum total thyroxine (TT4) concentration in euthyroid dogs. Six healthy beagle dogs were used in each of the 3 phases of this study. Phase I: thyroid-stimulating hormone response tests were performed by using a total dose of 25 micrograms, 50 micrograms, and 100 micrograms of rhTSH, administered intravenously. Phases II and III: thyroid-stimulating hormone response tests were performed by using 50 micrograms of rhTSH administered by intramuscular and subcutaneous routes, respectively. In each phase and following all the administered doses of rhTSH, an increase in the serum TT4 concentration was noted, although it was not always significant. For phase I, there was a significant increase in serum TT4 concentrations. Based on this study, 50 micrograms was judged to be the optimal intravenous dose of rhTSH. For phases II and III, there was no significant increase in serum TT4 after the administration of rhTSH. Results of this study suggest that rhTSH could be a good substitute for bovine TSH, when used by the intravenous route, for the TSH stimulation test in dogs. Further studies are required to confirm its clinical usefulness.