Pharmacokinetic evaluation of enrofloxacin administered orally to healthy dogs.

Enrofloxacin was administered orally to 6 healthy dogs at dosages of approximately 2.75, 5.5, and 11 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosage regimens. Serum and tissue cage fluid (TCF) concentrations of enrofloxacin were measured after the first and seventh treatments. The mean peak serum concentration occurred between 1 and 2.5 hours after dosing. Peak serum concentrations increased with increases in dosage. For each dosage regimen, there was an accumulation of enrofloxacin between the first and seventh treatment, as demonstrated by a significant (P = 0.001) increase in peak serum concentrations. The serum elimination half-life increased from 3.39 hours for the 2.75 mg/kg dosage to 4.94 hours for the 11 mg/kg dosage. Enrofloxacin accumulated slowly into TCF, with peak concentrations being approximately 58% of those of serum. The time of peak TCF concentrations occurred between 3.8 hours and 5.9 hours after drug administration, depending on the dosage and whether it was after single or multiple administrations. Compared with serum concentrations (area under the curve TCF/area under the curve serum), the percentage of enrofloxacin penetration into TCF was 85% at a dosage of 2.75 mg/kg, 83% at a dosage of 5.5 mg/kg, and 88% at a dosage of 11 mg/kg. All 3 dosage regimens of enrofloxacin induced continuous serum and TCF concentrations greater than the minimal concentration required to inhibit 90% (MIC90) of the aerobic and facultative anaerobic clinical isolates tested, except Pseudomonas aeruginosa.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of selenium administered parenterally at toxic doses in sheep

Pharmacokinetics of Se were evaluated in 24 female crossbred sheep, 8 to 14 months of age, after toxic doses of Se were administered. Five groups of 4 sheep each were given 0.4, 0.6, 0.7, 0.8, or 1 mg of Se/kg of body weight, IM. Nine of these sheep died within 36 hours after Se administration. Blood Se disappearance curves were triphasic for the 11 sheep that lived for at least 36 hours after Se administration and were biphasic for the 9 sheep that died within 36 hours. The lambda 2 rate constants of Se disposition after IM administration indicated a dose dependency. Sheep given 0.4, 0.6, 0.7, or 0.8 mg of Se/kg had lambda 2 rate constants of 0.110, 0.079, 0.046, and 0.034 hour-1, respectively (r2 = 0.97). The respective half-lives of the 2nd distributive phase after IM administration were 6.3, 8.8, 15.1, and 20.4 hours. In the 11 sheep that had triphasic pharmacokinetics, the mean lambda 3 elimination rate was 0.0011 hour-1. Four additional sheep were given 0.7 mg of Se/kg, IV. These sheep survived and had blood Se disappearance curves that were triphasic. In the 4 sheep given Se IV, the mean lambda 3 elimination rate was 0.0020 hour-1, which represented a biological half-life of 354 hours or 14.7 days.     

Effects of single-dose L-asparaginase on coagulation values in healthy dogs and dogs with lymphoma.

Ten healthy dogs and 10 dogs with multicentric lymphoma were given a single dose of L-asparaginase at a rate of 10,000 IU/m2 of body surface. Assessment of concentrations of contributors to the coagulation process and of the ability to coagulate including antithrombin III, one-stage prothrombin time, prothrombin-proconvertin time, activated partial thromboplastin time, plasminogen, fibrinogen, and platelet number were performed prior to drug administration (day 0). These tests were repeated 24 hours (day 1), 48 hours (day 2), and 7 days after treatment with L-asparaginase. Antithrombin-III concentrations were significantly lower in the dogs with lymphoma than in healthy dogs on days 0, 1, 2, and 7; however, with the exception of day 1, mean values remained within normal limits. There was also a difference between the 2 groups in prothrombin/proconvertin values on day 7 and in platelet number on day 2, with the lymphoma group having significantly shorter prothrombin/proconvertin time than healthy dogs, and the difference in platelet numbers being associated with increased counts in the healthy dogs. Data obtained from the healthy dogs and dogs with lymphoma for each coagulation test were pooled for each treatment day (0, 1, 2, and 7), and day-0 values for each coagulation test were compared with data obtained on days 1, 2, and 7. Antithrombin-III concentration on day 7 was significantly lower than on day 0, prothrombin/proconvertin time on day 1 was significantly longer than on day 0, and fibrinogen concentrations on days 1 and 2 were significantly lower than on day 0.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative hemodynamic effects of halothane and halothane-acepromazine at equipotent doses in dogs.

The purpose of this study was to compare the cardiovascular effects of halothane when used alone at increasing doses (1.2, 1.45 and 1.7 minimum alveolar concentration, MAC) to those produced with equipotent doses of halothane after potentiation of the anesthetic effect with acepromazine (ACP) sedation (45% reduction of halothane MAC). Six healthy mature dogs were used on three occasions. The treatments were halothane and intramuscular (IM) saline (1.0 mL), halothane and ACP (0.04 mg/kg IM), or halothane and ACP (0.2 mg/kg IM). Anesthesia was induced and maintained with halothane in oxygen and the dogs were prepared for the collection of arterial and mixed venous blood and for the determination of heart rate, systolic, diastolic and mean arterial pressure, mean pulmonary arterial pressure (PAP), central venous pressure and cardiac output. Following animal preparation the saline or ACP was administered and positive pressure ventilation instituted. Twenty-five minutes later the dogs were exposed to the first of three anesthetic levels, with random assignment of the sequence of administration. At each anesthetic level, measurements were obtained at 20 and 35 min. Calculated values included cardiac index, stroke index, left ventricular work, systemic vascular resistance, arterial oxygen content, mixed venous oxygen content, oxygen delivery and oxygen consumption. Heart rate was significantly higher with halothane alone than with both halothane-ACP combinations and was significantly higher with high dose ACP compared to low dose ACP. Systolic and mean blood pressures were lowest with halothane alone and highest with 0.2 mg/kg ACP, the differences being significant for each treatment. Oxygen uptake and PAP were significantly lower in dogs treated with ACP. It was concluded that ACP does not potentiate the cardiovascular depression that accompanies halothane anesthesia when the resultant lower dose requirements of halothane are taken into consideration.     

Preclinical evaluation of a liposome-encapsulated formulation of cisplatin in clinically normal dogs

OBJECTIVE: To determine the acute and short-term adverse effects of a liposome-encapsulated form of cisplatin at increasing dosages of up to twice the known maximally tolerated dose (MTD) of unencapsulated cisplatin in clinically normal dogs. ANIMALS: 4 healthy 2.5-year-old sexually intact female hound-type dogs. PROCEDURE: 4 dosages (70, 100, 125, and 150 mg/m2) were evaluated, and the 4 dogs received a total of 9 infusions (1 to 3 infusions/dog). Dogs were monitored to detect changes in clinical and clinicopathologic status. Evaluations consisting of a physical examination, CBC, serum biochemical analysis, and urinalysis were performed before and 7 and 21 days after each infusion. RESULTS: Acute anaphylactic-like reactions to liposome-encapsulated cisplatin were common but clinically manageable. Nephrotoxicosis and substantial myelosuppression, toxic effects commonly associated with unencapsulated cisplatin, were not observed in dogs treated with liposome-encapsulated cisplatin at dosages equivalent to twice the known MTD of unencapsulated cisplatin. CONCLUSIONS AND CLINICAL RELEVANCE: Liposome-encapsulated cisplatin can be safely administered to clinically normal dogs at dosages of up to 150 mg/m2 without the need for concurrent hydration protocols. This was a necessary prerequisite to enable phase I clinical trials in dogs with naturally developing cancers that could theoretically benefit from escalation in the dosage of cisplatin. Determination of an MTD, cumulative and long-term toxic effects, and efficacy can now be conducted in the context of phase I trials in tumor-bearing dogs.     

Prospective evaluation of a peripherally administered three-in-one parenteral nutrition product in dogs

OBJECTIVES: Peripheral parenteral nutrition is an option for short-term nutritional support in dogs which cannot be supported with enteral nutrition. The objective of this study was to examine the use of a three-in-one, 840 mOsmol/l peripheral parenteral nutrition product containing amino acids, lipids and glucose in separate compartments in dogs. METHODS: Nine dogs were administered the three-in-one product, and two dogs were administered the amino acid part of the product, via a peripheral vein. Dogs were monitored for mechanical and metabolic complications. RESULTS: Mechanical complications (apparent thrombus or thrombophlebitis) caused failure of infusion at a median of 36 hours. None of the dogs appeared to develop catheter-related sepsis. Using a 10-hour infusion period appeared to decrease the incidence of line failure. Mild and clinically non-significant hyperglycaemia was the only metabolic complication. In four of the dogs, serum folate, cobalamin and homocysteine concentrations were determined before and after peripheral parenteral nutrition administration. Oral and parenteral administration of methionine has been previously associated with lowered serum folate concentrations. Low serum folates and the subsequent hyperhomocysteinaemia have been associated with venous endothelial damage and venous thrombus in other species. Serum cobalamin also affects homocysteine metabolism. Median serum folate, cobalamin and homocysteine concentrations were not affected by the short-term administration of this three-in-one product. CLINICAL SIGNIFICANCE: Using the product for 24 hours/day may require catheter replacement due to line failure. Other than line failure, which may be improved by 10- to 12-hour infusion times, this product was found to be safe and practical for short-term peripheral parenteral nutrition in dogs.     

High-dose methotrexate and leucovorin rescue in dogs with osteogenic sarcoma.

Five dogs with ostoegenic sarcoma were treated by surgical removal of the primary tumor and by adjuvant chemotherapy. Methotrexate at dosages of 3 to 6 g/m2 was used with leucovorin rescue. All dogs tolerated E g of methotrexate/m2 of body surface, but granulocytopenia precluded escalation beyond this dosage in 4 dogs. The rate and time of appearance of pulmonary metastases were not altered by treatment, with all dogs developing metastases at a median time of 4 months after amputation.     

Effects of single intravenously administered doses of dexamethasone on response to the adrenocorticotropic hormone stimulation test in dogs

The effects of single IV administered doses of dexamethasone on response to the adrenocorticotropic hormone (ACTH) stimulation test (baseline plasma ACTH, pre-ACTH cortisol, and post-ACTH cortisol concentrations) performed 1, 2, and 3 days (experiment 1) or 3, 7, 10, and 14 days (experiment 2) after dexamethasone treatment were evaluated in healthy Beagles. In experiment 1, ACTH stimulation tests were carried out after administration of 0, 0.01, 0.1, 1, and 5 mg of dexamethasone/kg of body weight. Dosages greater than or equal to 0.1 mg of dexamethasone/kg decreased pre-ACTH plasma cortisol concentration on subsequent days, whereas dosages greater than or equal to 1 mg/kg also decreased plasma ACTH concentration. Treatment with 1 or 5 mg of dexamethasone/kg suppressed (P less than 0.05) post-ACTH plasma cortisol concentration (on day 3 after 1 mg of dexamethasone/kg; on days 1, 2, and 3 after 5 mg of dexamethasone/kg). In experiment 2, IV administration of 1 mg of dexamethasone/kg was associated only with low (P less than 0.05) post-ACTH plasma cortisol concentration in dogs on day 3. In experiment 2, pre-ACTH plasma cortisol and ACTH concentrations in dogs on days 3, 7, 10, and 14 and post-ACTH plasma cortisol concentration on days 7, 10, and 14 were not affected by dexamethasone administration. The results suggest that, in dogs, a single IV administered dosage of greater than or equal to 0.1 mg of dexamethasone/kg can alter the results of the ACTH stimulation test for at least 3 days. The suppressive effect of dexamethasone is dose dependent and is not apparent 7 days after treatment with 1 mg of dexamethasone/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of low doses of ketamine administered by constant rate infusion as an adjunct for postoperative analgesia in dogs

OBJECTIVE: To compare indicators of postoperative pain and behavior in dogs with and without a low-dose ketamine infusion added to usual perioperative management. DESIGN: Prospective, randomized, blinded clinical study. ANIMALS: 27 dogs undergoing forelimb amputation. PROCEDURE: Dogs were anesthetized with glycopyrrolate, morphine, propofol, and isoflurane. Thirteen dogs were treated with ketamine IV, as follows: 0.5 mg/kg (0.23 mg/lb) as a bolus before surgery, 10 microg/kg/min (4.5 microg/lb/min) during surgery, and 2 microg/kg/min (0.9 microg/lb/min) for 18 hours after surgery. Fourteen dogs received the same volume of saline (0.9% NaCl) solution. All dogs received an infusion of fentanyl (1 to 5 microg/kg/h [0.45 to 2.27 pg/lb/h]) for the first 18 hours after surgery. Dogs were evaluated for signs of pain before surgery, at the time of extubation, and 1, 2, 3, 4, 12, and 18 hours after extubation. Owners evaluated their dogs' appetite, activity, and wound soreness on postoperative days 2, 3, and 4. RESULTS: Dogs that received ketamine infusions had significantly lower pain scores 12 and 18 hours after surgery and were significantly more active on postoperative day 3 than dogs that received saline solution infusions. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that perioperative administration of low doses of ketamine to dogs may augment analgesia and comfort in the postoperative surgical period.     

Effect of topically administered atropine on tear production in dogs.

Baseline tear production values were established for both eyes of 19 dogs, using the Schirmer tear test. Atropine sulfate, 1% solution, was administered topically in the left eye of each dog once daily for 14 days. Tear production was then determined for both eyes at 15, 30, 60, 120, 180, 240, and 300 minutes, and 3, 6, 9, 12, and 15 days. A final Schirmer tear test reading was obtained for each eye 5 weeks after the last atropine treatment to check for the possibility of prolonged effect. Both eyes had statistically significant (P less than 0.05) decrease in tear production that was most marked at 120 minutes after atropine instillation, then returned to baseline values by 300 minutes after instillation. Although atropine was placed in the left eye only, statistically significant difference was not apparent in Schirmer tear test values between the left and right eyes. Tear production continued to decrease in both eyes over time, becoming statistically significant (P less than 0.05) on day 9. However, on days 12 and 15, tear production in the untreated eye plateaued, but that in the treated eye continued to decrease. Five weeks after the last treatment with atropine, both eyes still had a statistically significant (P less than 0.05) decrease in tear production, although Schirmer tear test values had increased from day-15 values and appeared to be returning to baseline. Association was not evident between age or body weight and magnitude of response to topically applied atropine.     

Serum pharmacokinetics of clindamycin hydrochloride in normal dogs when administered at two dosage regimens

The aim of this cross-over study was to compare clindamycin pharmacokinetics in the serum of clinically normal dogs when administered orally at two dosage regimens (5.5 mg/kg, twice daily, and 11 mg/kg, once daily), separated by a 1 week wash-out period. Serum samples were obtained from six clinically normal laboratory beagles before, 3, 6, 9 and 12 h after the first and fifth dose of clindamycin at 5.5 mg/kg, twice daily, and before, 3, 6, 9, 12, 18 and 24 h after the first and third dose at 11 mg/kg, once daily. Serum clindamycin concentrations were determined by reverse-phase liquid chromatography coupled with mass spectrometry. Results were analysed using Student's paired t-test, at a 5% level of significance. Values of pharmacokinetic parameters that differed significantly between the two dosage regimens included the following: maximal concentration and area under the concentration-time curve were higher at 11 mg/kg, once daily, than at 5.5 mg/kg, twice daily; and, more importantly, the ratio of AUC(0-24) to the minimal inhibitory concentration (MIC) value of 0.5 μg/mL for a 24 h period (AUC(0-24)/MIC) was higher when clindamycin was administered at 11 than at 5.5 mg/kg, at least during the first day of drug administration. Therefore, a better pharmacokinetic profile may be expected when clindamycin is administered at 11 mg/kg, once daily, for the treatment of canine pyoderma caused by Staphylococcus pseudintermedius.     

Phase I and pharmacokinetic evaluation of the combination of orally administered docetaxel and cyclosporin A in tumor-bearing dogs

OBJECTIVE: To determine the maximum tolerated dose and characterize the pharmacokinetic disposition of an orally administered combination of docetaxel and cyclosporin A (CSA) in dogs with tumors. ANIMALS: 16 client-owned dogs with metastatic or advanced-stage refractory tumors. PROCEDURES: An open-label, dose-escalation, single-dose, phase I study of docetaxel administered in combination with a fixed dose of CSA was conducted. Docetaxel (at doses of 1.5, 1.625, or 1.75 mg/kg) and CSA (5 mg/kg) were administered concurrently via gavage twice during a 3-week period. Plasma docetaxel concentrations were quantified by use of high-performance liquid chromatography, and pharmacokinetic disposition was characterized by use of noncompartmental analysis. Dogs' clinical signs and results of hematologic and biochemical analyses were monitored for evidence of toxicosis. RESULTS: No acute hypersensitivity reactions were observed after oral administration of docetaxel. Disposition of docetaxel was dose independent over the range evaluated, and pharmacokinetic variables were similar to those reported in previous studies involving healthy dogs, with the exception that values for clearance were significantly higher in the dogs reported here. The maximum tolerated dose of docetaxel was 1.625 mg/kg. Gastrointestinal signs of toxicosis were dose limiting. CONCLUSIONS AND CLINICAL RELEVANCE: The absence of myelosuppression suggested that the docetaxel-CSA combination may be administered more frequently than the schedule used. Further studies are warranted to evaluate combination treatment administered on a biweekly schedule in dogs with epithelial tumors.     

Safety evaluation of orally administered afoxolaner and milbemycin oxime in eight‐week‐old dogs

The safety profile of afoxolaner (an isoxazoline molecule) when combined with milbemycin oxime (a macrocyclic lactone) was evaluated according to the regulatory requirements when administered six times orally in a soft chewable formulation at a dose of at least 1×, 3×, or 5× the maximum exposure dose in 8‐week‐old Beagle dogs. Thirty‐two healthy puppies (16 males and 16 females) were enrolled and allocated randomly to one of four treatment groups. Three doses were administered at 28‐day intervals (Days 0, 28, and 56), followed by three additional doses administered with 14‐day intervals (Days 84, 98, and 112). The study ended on Day 126. Treatment groups were as follows: Group 1: untreated, sham‐dosed control; Group 2: afoxolaner/milbemycin oxime chews administered at a dose of at least 5 and 1 mg/kg, respectively (1×); Group 3: afoxolaner/milbemycin oxime chews administered at a dose of at least 15 and 3 mg/kg, respectively (3); and Group 4: afoxolaner/milbemycin oxime chews administered at a dose of at least 25 and 5 mg/kg, respectively (5×). All dogs were examined for general health twice a day beginning on Day ‐14. Physical examinations, and blood collections for clinical pathology analysis and afoxolaner and milbemycin oxime plasma concentrations, were performed throughout the study. No afoxolaner/milbemycin oxime treatment‐related changes were observed in growth, physical variables, clinical pathology variables, or tissues examined histologically. No clinically relevant or statistically significant health abnormalities related to the administration of afoxolaner/milbemycin oxime were observed. No signs of macrocyclic lactone sensitivity were observed at any time during the study. Vomiting and diarrhea were observed sporadically across all groups including the controls. Based upon the results of this study, afoxolaner/milbemycin oxime soft chewables were shown to be safe when administered repeatedly at up to 5× the maximum exposure dose in dogs as young as 8 weeks of age.     

Interaction between epidurally administered ketamine and pethidine in dogs

The present study was designed to test the hypothesis that a synergistic interaction could be recorded after epidural administration of ketamine-an N-methyl-D-aspartate (NMDA) antagonist and pethidine--an opioid agonist. Twelve adult mongrel dogs of either sex were randomly divided in three groups A, B and C of four animals each. Ketamine (5%) at 2.5 mg/kg and pethidine (3%) 2 mg/kg were injected at lumbosacral epidural space in animals of groups A and B, respectively. In animals of group C ketamine (2.5 mg/kg) and pethidine (2 mg/kg) were injected. Heart rate increased significantly up to 15 min in group A, whereas in groups B and C, the increase was non-significant for a period of 10 and 45 min, respectively. Respiration increased gradually up to 45-60 min in group A and for 15-20 min in group B. However, in animals of group C respiration fell below the baseline during the first 10-15 min and then returned near the baseline. Rectal temperature decreased only marginally in all the groups. Ketamine alone produced complete analgesia at tail and perineal region for a period of 5-10 min and then moderate analgesia for the next 20-30 min. Analgesia at the flank was moderate to complete between 5 and 15 min. In group B complete analgesia was only moderate at the tail and perineal region up to 30 min. In animals of group C, complete analgesia was observed only at perineal region for a very short period (5 min). Analgesia was not associated with sedation in any of the groups but animals of groups A and C showed signs of motor incoordination. Results of the study suggest rather antagonistic than synergistic interaction between epidurally administered ketamine and pethidine. Further studies are needed to confirm the antagonistic interaction between the two drugs.     

Gastric hemorrhage in dogs given high doses of methylprednisolone sodium succinate.

OBJECTIVE: To determine whether healthy dogs given high doses of methylprednisolone sodium succinate (MPSS) develop gastrointestinal tract ulcers and hemorrhage. ANIMALS: 19 healthy male hound-type dogs. PROCEDURE: Dogs were assigned randomly to intravenously receive high doses of MPSS (30 mg/kg of body weight, initially, then 15 mg/kg 2 and 6 hours later, and, subsequently, every 6 hours for a total of 48 hours; n = 10) or an equal volume of saline (0.9% NaCl) solution (9). Gastroduodenoscopy was performed before and after treatment. Endoscopic evidence of gross hemorrhage in the cardia, fundus, antrum, and duodenum of each dog was graded from none (0) to severe (3), and a total stomach score was calculated as the sum of the regional gastric scores. Number of ulcers were recorded. The pH of gastric fluid and evidence of occult gastric and fecal blood were measured. Food retention was recorded. RESULTS: Gastric hemorrhage was evident in all dogs after MPSS administration and was severe in 9 of 10 dogs but not visible in any dog after saline treatment. Occult gastric blood was detected more commonly (9/10 vs 2/9), median gastric acidity was greater (pH 1 vs pH 3), and food was retained more commonly (7/10 vs 1/9) in the stomach of MPSS-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE: High doses of MPSS cause gastric hemorrhage in dogs. All dogs treated with high doses of MPSS should be treated with mucosal protectants or antacids to prevent gastric hemorrhage.     

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)     

Effects of medetomidine and buprenorphine administered for sedation in dogs

Medetomidine at doses of 10, 20 or 30 microg/kg was administered along with 10 microg/kg buprenorphine intramuscularly to 48 dogs requiring sedation for various diagnostic or therapeutic procedures. The heart rate, respiratory rate and degree of sedation were recorded before and 30 minutes after administration of the drugs. Heart rate fell by a mean of 55 per cent and respiratory rate by a mean of 62 per cent. Mean sedation scores were increased in all groups. Administration of atipamezole at the end of the period of sedation produced rapid recoveries, with a mean time to standing of 12 minutes. Animals that were anaesthetised required much less thiopentone than the 10 mg/kg recommended after premedication with acepromazine maleate.     

Biovailability of ivermectin administered orally to dogs

The bioavailability of three formulations of ivermectin was determined following oral administration to dogs. The average peak plasma level (C _max) of ivermectin administered in the standard tablet formulation at 6 and 100 µg/kg of body weight was 2.97 and 44.31 ng/g, respectively. This suggest dose-dependent pharmacokinetics.C _max and total ivermectin bioavailability, as assessed from the area under the plasma curve (AUC), were similar between two tablet formulations of ivermectin administered at 100 µg/kg. Furthermore,C _max was similar following administration of radiolabelled ivermectin at 6 µg/kg in either a beef-based chewable formulation or in the standard tablet formulation.