Evaluation of concentration of voriconazole in aqueous humor after topical and oral administration in horses

OBJECTIVE: To determine penetration of topically and orally administered voriconazole into ocular tissues and evaluate concentrations of the drug in blood and signs of toxicosis after topical application in horses. ANIMALS: 11 healthy adult horses. PROCEDURE: Each eye in 6 horses was treated with a single concentration (0.5%, 1.0%, or 3.0%) of a topically administered voriconazole solution every 4 hours for 7 doses. Anterior chamber paracentesis was performed and plasma samples were collected after application of the final dose. Voriconazole concentrations in aqueous humor (AH) and plasma were measured via high-performance liquid chromatography. Five horses received a single orally administered dose of voriconazole (4 mg/kg); anterior chamber paracentesis was performed, and voriconazole concentrations in AH were measured. RESULTS: Mean +/- SD voriconazole concentrations in AH after topical administration of 0.5%, 1.0%, and 3.0% solutions (n = 4 eyes for each concentration) were 1.43 +/- 0.37 microg/mL, 2.35 +/- 0.78 microg/mL, and 2.40 +/- 0.29 microg/mL, respectively. The 1.0% and 3.0% solutions resulted in significantly higher AH concentrations than the 0.5% solution, and only the 3.0% solution induced signs of ocular toxicosis. Voriconazole was detected in the plasma for 1 hour after the final topically administered dose of all solutions. Mean +/- SD voriconazole concentration in AH after a single orally administered dose was 0.86 +/- 0.22 microg/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that voriconazole effectively penetrated the cornea in clinically normal eyes and reached detectable concentrations in the AH after topical administration. The drug also penetrated noninflamed equine eyes after oral administration. Low plasma concentrations of voriconazole were detected after topical administration.     

Effects of storage on concentration of hydrocortisone (cortisol) in canine serum and plasma

A specific radioimmunoassay was used to measure concentrations of hydrocortisone (cortisol) in the serum and plasma of 4 dogs. Differences (P greater than 0.05) in concentrations of cortisol were not found between serum and plasma (from EDTA-treated and heparinized blood samples). Differences (P greater than 0.05) in serum or plasma concentrations of cortisol were not found between samples stored at 4 C for various times (10 minutes, 10 hours, 40 hours) after collection, but before removal of RBC. In a study designed to determine the stability of cortisol in serum samples stored at room temperature, degradation was dependent on the initial serum concentrations of cortisol. Decreases (P greater than 0.05) did not occur in concentrations of cortisol in serum samples stored up to 15 days when initial concentrations of cortisol were less than 15 ng/ml. However, when initial concentrations of cortisol were approximately 55 ng/ml and 80 ng/ml, significant (P greater than 0.05) degradation occurred after 9 and 5 days of storage, respectively. Results of this investigation indicate that either serum or plasma of dogs is suitable for radioimmunoassay of cortisol and that samples (with and without added coagulants) incubated at 4 C may be left uncentrifuged for up to 40 hours without cortisol degradation. However, prolonged storage of serum at room temperature is detrimental, particularly for samples having large concentrations of cortisol.     

Canine plasma cortisol (hydrocortisone) measured by radioimmunoassay: clinical absence of diurnal variation and results of ACTH stimulation and dexamethasone suppression tests.

A radioimmunoassay for plasma cortisol (hydrocortisone) was developed and validated for sensitivity, specificity, accuracy, precision, and parallelism. Steroids were extracted with ethyl ether, and cortisol was purified by gel column chromatography prior to assay. [1,2-3H] cortisol and a commercially available sheep antibody to cortisol-21-hemisuccinate were used. Free steriods were separated from bound steroids by centrifugation after adsorption to dextran-coated charcoal. Plasma cortisol was measured by this technique in 6 normal dogs. Circadian rhythm of cortisol secretion was not detected in samples obtained by venipuncture at 8 different hours on 3 separate days, suggesting that adrenal function tests may be started in clinical patients at any time of day. Resting plasma cortisol concentrations averaged 19.4+/-3.0 (SD) ng/ml and ranged from nondetectable (less than 3 ng/ml) to 77.5 ng/ml. Of 144 canine plasma samples, 95% contained less than 50 ng of cortisol/ml. Intramuscular injection of 2.2 units of adrenocorticotropic hormone/kg of body weight caused detectable increase in plasma cortisol concentrations; maximum response (68.3 to 111.6 ng/ml) occurred 1 to 2 hours after injection. Oral administration of dexamethasone suppressed plasma cortisol to nondetectable concentrations for 32 hours in all 6 dogs.     

Comparison of histamine release induced by morphine and oxymorphone administration in dogs

Cardiovascular effects (vasodilatation, hypotension) of morphine administration have been attributed to central actions and peripheral histamine release. In the study reported here, we compared plasma histamine (Hm) concentrations after morphine sulfate and oxymorphone HCl administration in conscious dogs. Five healthy adult dogs (mean body weight, 10.1 kg) were randomly administered morphine (2 mg/kg of body weight, IV) or oxymorphone (0.2 mg/kg, IV) by a 5-second bolus injection at weekly intervals. Venous blood samples (5 ml) were collected from jugular veins before and at 1, 2, 5, 15, 30, and 60 minutes after drug administration. Behavioral changes were recorded. Plasma was analyzed by a radioenzymatic technique, using purified histamine N-methyltransferase as an enzyme catalyst (sensitivity of assay, 40 pg Hm/ml). Mean base-line Hm value for all dogs was 0.55 ng/ml. The mean Hm value was significantly higher (P less than 0.05) than the base-line value at 1, 2, 5, 15, and 60 minutes after morphine administration (531.4, 251.0, 113.0, 31.5, and 1.0 ng of Hm/ml, respectively), but there were no significant increases in histamine values from base-line values at any time after oxymorphone administration. All dogs given morphine and 1 dog given oxymorphone showed excitatory behavior; 2 dogs given morphine and 3 dogs given oxymorphone salivated profusely.     

Effect of exogenous ACTH on serum corticosterone and cortisol concentrations in the Moluccan cockatoo (Cacatua moluccensis)

The effects of exogenous adrenocorticortrophic hormone (ACTH) on the serum corticosterone and cortisol concentrations were determined in 28 mature Moluccan cockatoos (Cacatua moluccensis), a representative of the psittacine species. Birds were randomly assigned to 4 groups (2 ACTH-treated groups and 2 saline-treated controls). Group I (10 cockatoos [5 males and 5 females] ) was given 15 IU of ACTH after blood samples (base line) were taken at 10:00 AM. Blood samples were taken again at 30 minutes and 2.5 hours after ACTH administration. Group II (10 cockatoos) was given similar treatment, but blood samples were taken at 1 and 4 hours after ACTH was administered. Groups III and IV (each of 4 birds) were given saline solution injections as controls. Blood samples were taken at 30 minutes and 2.5 hours after injection (group III) and at 1 and 4 hours after injection (group IV). All serum samples were analyzed for cortisol and corticosterone. Serum corticosterone concentration increased significantly (P less than 0.01) from base-line levels (26 ng/ml) to 108 ng/ml within 30 minutes after ACTH was administered. The high values were maintained for 3 hours and then decreased to 40 ng/ml at the end of 4 hours. Male birds seemed to respond to the ACTH treatment quickly and maintained increased concentration for a shorter period when compared with the responses seen in female birds. Serum cortisol values remained low throughout the experimental period. These results indicate that serum corticosterone was responsive to ACTH administration, but cortisol was not. In addition, there may be a difference in the responses between male and female members of the species.     

Effect of lysine-acetylsalicylate and phenylbutazone premedication on the protein content of secondary aqueous humour in the dog

Inhibitory effects of the anti-inflammatory agents lysine-acetylsalicylate (LAS) and phenylbutazone (PBZ) on the breakdown of the blood-aqueous barrier by paracentesis were studied in canine eyes using protein determination of ocular fluid. In the untreated eyes the aqueous protein value was raised from 0.29 +/- 0.17 (mean +/- SD) g litre-1 at the initial paracentesis to 14.47 +/- 4.10 g litre-1 at the second paracentesis. Pretreatment with LAS or PBZ had no significant effect on the protein concentration of the primary aqueous humour. However the secondary aqueous protein concentration was only 10.05 +/- 7.00 g litre-1 with LAS and 5.80 +/- 3.83 g litre-1 with PBZ. With both drugs the maximum inhibitory effect was observed on the gammaglobulins and albumin. These results suggest that prostaglandins may be involved in the response of the canine eye to paracentesis and that premedication with LAS or PBZ may be of value in reducing postoperative ocular inflammation.     

Evaluation of progesterone deficiency as a cause of fetal death in mares with experimentally induced endotoxemia

The role of decreased luteal activity in embryonic loss after induced endotoxemia was studied in mares 21 to 35 days pregnant. Fourteen pregnant mares were treated daily with 44 mg of altrenogest to compensate for the loss of endogenous progesterone secretion caused by prostaglandin F2 alpha (PGF2 alpha) synthesis and release following intravenous administration of Salmonella typhimurium endotoxin. Altrenogest was administered daily from the day of endotoxin injection until day 40 of gestation (group 1; n = 7), until day 70 (group 2; n = 5), or until day 50 (group 3; n = 2). In all mares, secretion of PGF2 alpha, as determined by the plasma 15-keto-13,14-dihydro-PGF2 alpha concentrations, followed a biphasic pattern, with an initial peak at 30 minutes followed by a second, larger peak at 105 minutes after endotoxin injection. Plasma progesterone concentrations decreased in all mares to values less than 1 ng/ml within 24 hours after endotoxin injection. In group 1, progesterone concentrations for all mares were less than 1 ng/ml until the final day of altrenogest treatment. In 6 of 7 mares in group 1, the fetuses died within 4 days after the end of treatment, with progesterone concentrations less than 1 ng/ml at that time. In the mare that remained pregnant after the end of treatment, plasma progesterone concentration was 1.6 ng/ml on day 41 and increased to 4.4 ng/ml on day 44. In group 2, all mares remained pregnant, even though plasma progesterone concentrations were less than 1 ng/ml in 4 of 5 mares from the day after endotoxin injection until after the end of altrenogest treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tolfenamic acid in the control of ocular inflammation in the dog: Pharmacokinetics and clinical results obtained in an experimental model

Tolfenamic acid (TA) was tested in two studies to investigate its value in controlling ocular inflammation in the dog. First, TA was assayed within primary and secondary aqueous humour (AH) and in plasma 0, 4 and 24 hours after a 4 mg/kg subcutaneous injection. Secondly, an experimental ocular surgery model was set up in 10 dogs - five receiving TA two hours before surgery and five left untreated. TA was shown to diffuse into AH, reaching lower levels than in plasma: 1:126 ratio in primary AH and 1:43 in secondary AH. In the model, TA-treated dogs versus untreated dogs showed a significant reduction of miosis (P< 0–05) and a clear trend to a reduced ocular discharge and corneal oedema (P=0–06). Prostaglandin E₂ (PGE₂) levels increased significantly less in AH after TA treatment (P<0–05). These results show that TA, even if the whole concentration measured in AH is lower than in plasma, is able to limit the synthesis of the inflammatory mediator PGE₂ in AH and to control ocular inflammatory symptoms induced by corneal surgery.     

Effects of chronic gonadotropin-releasing hormone agonist treatment on serum luteinizing hormone and testosterone concentrations in boars.

Mature boars were subjected to chronic treatment with a gonadotropin-releasing hormone (GnRH) agonist, goserelin (D-Ser[But]6, Azgly-NH210), and serum luteinizing hormone (LH) and testosterone concentrations were measured. Ten sexually mature boars were randomly assigned to treatment (n = 5) or control (n = 5) groups. On day 0, boars were implanted sc (day 0) with 2 GnRH agonist implants (1 mg of GnRH/implant) or sham implants. Blood samples were collected at 12-hour intervals on days -2 and -1, at 6-hour intervals on days 0 through 4, and at 12-hour intervals on days 5 through 8. In addition, blood samples were collected at 15-minute intervals for 6 hours on days -1, 0, 4, and 8. Serum testosterone and LH concentrations were determined by radioimmunoassay. Maximal LH (7 +/- 1 ng/ml) and testosterone (26 +/- 3 ng/ml) concentrations were observed at 5 and 18 hours, respectively, after GnRH agonist treatment. Subsequently, LH and testosterone concentrations decreased to pretreatment values (0.3 +/- 0.1 ng/ml and 1.8 +/- 0.4 ng/ml, respectively) by 24 and 48 hours, respectively, after GnRH agonist implantation. Few differences in the characteristics of pulsatile LH release were observed between the groups. Testosterone and LH concentrations in samples collected at 6- and 12-hour intervals and pulsatile LH release did not change after sham treatment of control boars. Whereas previous reports indicated that chronic GnRH administration suppressed serum LH and testosterone concentrations in rams, rats, and dogs, our results indicate that chronic GnRH agonist treatment induced transitory increases, without subsequent suppression, in LH and testosterone concentrations in mature boars.     

Dosing regimen and hematologic effects of pentoxifylline and its active metabolites in normal dogs

The disposition of pentoxifylline and two of its active metabolites (metabolite 1 [M1] and metabolite 5 [M5]) were studied following i.v. (8 mg/kg) and p.o. (30 mg/kg) administration to eight normal dogs using a randomized crossover design. Blood samples were collected at fixed time intervals after drug administration for determination of drug concentrations, platelet aggregation, and plasma fibrinogen. Complete blood counts, serum chemistry profiles, fibrinogen, and urinalysis were monitored at the beginning and end of each phase of the study (p.o. versus i.v. administration). Pentoxifylline was readily metabolized and bioavailable (50% +/- 26%). Both M1 and M5 were present throughout the study, with M5 predominating. Human drug therapeutic concentrations (1,000 ng/ml) were present for 170 +/- 24 minutes following i.v. administration and 510 +/- 85 minutes after p.o. dosing. These findings suggest that a 12-hour dosing regimen is appropriate. None of the dogs experienced any adverse effects after pentoxifylline administration. The lack of hematologic effects suggests that the immunologic effects of pentoxifylline may be of more importance in dogs.     

Lontophoretic administration of dexamethasone into the tarsocrural joint in horses

OBJECTIVE: To determine whether iontophoretic administration of dexamethasone to horses results in detectable concentrations in synovial fluid, plasma, and urine. ANIMALS: 6 adult mares. PROCEDURE: Iontophoresis was used to administer dexamethasone. Treatments (4 mA for 20 minutes) were administered to a tarsocrural joint of each mare. The drug electrode contained 3 ml of dexamethasone sodium phosphate at a concentration of 4 or 10 mg/ml. Samples of synovial fluid, blood, and urine were obtained before and 0.5, 4, 8, and 24 hours after each treatment. All samples were tested for dexamethasone using an ELISA. Synovial fluid also was evaluated for dexamethasone, using high-performance liquid chromatography. RESULTS: The lower and upper limits of detection for dexamethasone in synovial fluid with the ELISA were 0.21 and 1.5 ng/ml, respectively. Dexamethasone administered at a concentration of 10 mg/ml was detected by the ELISA in synovial fluid of 5 mares from 0.5 to 24 hours and in urine of 4 mares from 0.5 to 8 hours after each treatment, but it was not detected in plasma. Mean synovial fluid concentration of dexamethasone was 1.01 ng/ml. Dexamethasone administered at a concentration of 4 mg/ml was detected by the ELISA in urine of 2 mares at 0.5 and 4 hours after treatment, but it was not detected in synovial fluid or plasma. CONCLUSIONS AND CLINICAL RELEVANCE: Iontophoresis cannot be considered an effective method for delivery of dexamethasone to synovial fluid of horses, because drug concentrations achieved in this study were less than therapeutic concentrations.     

Pharmacokinetics of sodium cephapirin in lactating dairy cows

Sodium cephapirin was administered (10 mg/kg of body weight, IM) at 8-hour intervals in 4 consecutive doses to each of 6 lactating dairy cows. Blood, normal milk, mastitic milk, urine, and endometrial tissue samples were collected serially. Mean peak cephapirin concentrations in serum were 13.3 micrograms/ml 10 minutes after the 1st injection and were 15.8 micrograms/ml 20 minutes after the 4th injection (post[initial]injection hour [PIH] 24.33). The overall elimination rate constant value was 0.66/h and plasma clearance was 760 ml/h/kg. Mean peak cephapirin concentration in normal milk was 0.11 microgram/ml at PIH 2 and mean peak cephapirin concentration in mastitic milk was 0.18 microgram/ml at PIH 4. Cephapirin was not detected in the endometrium. The highest concentration of cephapirin in urine was 452 micrograms/ml, 2 hours after the 4th dose (PIH 26).     

Laser flaremetric evaluation of experimentally induced blood-aqueous barrier disruption in cats

OBJECTIVES: To determine whether aqueous humor flare, measured by use of laser flaremetry, was proportional to aqueous humor protein concentration and to use laser flaremetry to evaluate disruption of the blood-aqueous barrier (BAB) in cats. ANIMALS: 30 healthy adult cats. PROCEDURE: Laser flaremetry values for all eyes were compared with aqueous humor protein concentrations determined by use of a Coomassie blue microprotein assay. Laser flaremetry was then performed on both eyes before (0 hours) and 4, 8, and 26 hours after initiation of topical application of 2% pilocarpine (q 8 h) to 1 eye of 9 cats or paracentesis of the anterior chamber of 1 eye of 8 cats. Intraocular pressure and pupil size were also determined. Aqueous humor protein concentration was extrapolated from flare values by use of linear regression. RESULTS: There was a linear relationship between flare values and aqueous humor protein concentrations. Topical application of 2% pilocarpine and paracentesis of the anterior chamber caused a breakdown of the BAB that was detected by use of laser flaremetry. The highest mean flare readings after application of pilocarpine or paracentesis were 24.4 and 132.8 pc/ms, respectively, which corresponded to aqueous humor protein concentrations of 85.5 and 434.9 mg/dl, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Paracentesis of the anterior chamber resulted in a more severe breakdown of the BAB in cats than topical application of 2% pilocarpine. Laser flaremetry may be a useful clinical method to detect increases in aqueous flare and, hence, disruptions of the BAB in cats.     

Passage of exogenous L-thyroxine and triiodothyronine into bovine ejaculate

The metabolic effects of thyroxine (T4) and triiodothyronine (T3) on spermatozoa metabolism and male anatomy have been demonstrated. The metabolic effects of T3 and T4 could affect the physiologic characteristics of the spermatozoa. There are little data on the passage of T4 and T3 into the ejaculate from blood. The passage of exogenous T4 and T3 from the blood into semen was measured after T4 (45 mg) or T3 (37.5 mg) was injected IV into 8 bulls. Blood and electroejaculate were obtained simultaneously at 20, 40, 60, 120, and 180 minutes and 24 hours after bulls were injected to determine T3 and T4 concentrations compared with base-line values. Blood T3 and T4 concentrations were increased (P less than 0.05) at 20 minutes after bulls were injected (1.1 +/- 0.25 to 598 +/- 76.3 ng/ml and from 66 +/- 5 to 1,318 +/- 105 ng/ml, respectively). Seminal concentrations of T4 were unchanged until 120 minutes after bulls were injected, when they increased (P less than 0.05) from less than 1.2 ng/ml to 4.7 +/- 1.9 ng/ml. However, seminal concentrations of T3 were increased (P less than 0.05) from less than 0.1 ng/ml to 0.5 +/- 0.2 ng/ml at 20 minutes and to 12.5 +/- 2.9 ng/ml at 120 minutes after bulls were injected. It was concluded that exogenous thyroid hormones passed into the ejaculate from blood, with T3 passing faster than T4.     

Serum concentrations of thyroxine and 3,5,3'-triiodothyronine before and after intravenous or intramuscular thyrotropin administration in dogs

Response to thyrotropin (TSH) was evaluated in 2 groups of mixed-breed dogs. Thyrotropin (5 IU) was administered IV to dogs in group 1 (n = 15) and IM to dogs in group 2 (n = 15). Venous blood samples were collected immediately before administration of TSH and at 2-hour intervals for 12 hours thereafter. In group 1, the maximum mean concentration (+/- SD) of thyroxine (T4; 7.76 +/- 2.60 micrograms/dl) and 3,5,3'-triiodothyroxine (T3; 1.56 +/- 0.51 ng/ml) was attained at postinjection hours (PIH) 8 and 6, respectively. However, the mean concentration of T4 at PIH 6 (7.21 +/- 2.39 micrograms/dl) was not different (P greater than 0.05) from the mean concentration at PIH 8. The maximum mean concentration of T4 (10.10 +/- 3.50 micrograms/dl) and T3 (2.22 +/- 1.24 ng/ml) in group 2 was attained at PIH 12 and 10, respectively. Because dogs given TSH by the IM route manifested pain during injection, had variable serum concentrations of T3 after TSH administration, and may require 5 IU to achieve maximal increases in serum T4 concentrations, IV administration of TSH is recommended. The optimal sampling time to observe maximal increases in T3 and T4 after IV administration of TSH was 6 hours. Repeat IV administration of TSH may cause anaphylaxis and, therefore, is not recommended.     

Serum disposition of exogenous progesterone after intramuscular administration in bitches

Progesterone was administered IM to 6 adult anestrous bitches at a dosage of 2 mg/kg of body weight. Serum progesterone concentrations were measured prior to progesterone administration and for 72 hours thereafter. The serum progesterone concentration time data were analyzed by use of a pharmacokinetics modeling computer program. The mean (+/- SD) peak serum progesterone concentration (34.3 +/- 7.8 ng/ml) was reached at 1.8 +/- 0.2 hours after progesterone administration. The mean serum progesterone concentration was 6.9 +/- 1.4 ng/ml at 24 hours and 2.0 +/- 0.4 ng/ml at 48 hours after progesterone administration. By 72 hours after administration, mean serum progesterone concentration was 0.9 +/- 0.2 ng/ml, which was comparable to serum progesterone concentrations prior to injection. The mean half-life of the absorption phase was 0.5 hours (range, 0.3 to 0.7 hours). The mean half-life of elimination was 12.1 hours (range, 9.5 to 13.8 hours). By analysis of the data, it was established that a dosage of 3 mg/kg, when the hormone was given IM to dogs once a day, would maintain serum progesterone concentration greater than 10 ng/ml.     

Effect of body position on intraocular pressure in dogs without glaucoma

OBJECTIVE: To determine the effects of body position on intraocular pressure (IOP) in dogs without glaucoma. ANIMALS: 24 healthy dogs with no evidence of glaucoma. PROCEDURES: Dogs underwent ophthalmic examinations to ensure that no IOP-affecting ocular diseases were present. Each dog was sequentially placed in dorsal recumbency, sternal recumbency, and sitting position. For each of the 3 positions, IOP in the right eye was measured by use of an applanation tonometer immediately after positioning (0 minutes) and after 3 and 5 minutes had elapsed. The initial body position was randomly assigned; each position followed the other positions an equal number of times, and IOP measurements were initiated immediately after moving from one body position to the next. Proparacaine hydrochloride (0.5%) was applied to the right eye immediately prior to IOP measurements. RESULTS: Intraocular pressure was affected by body position. During the 5-minute examination, IOP decreased significantly in dogs that were dorsally recumbent or sitting but did not change significantly in dogs that were sternally recumbent. For the 3 positions, overall mean IOP differed significantly at each time point (0, 3, and 5 minutes). Mean IOP in dorsal recumbency was significantly higher than that in sternal recumbency at 0 and at 3 minutes; although the former was also higher than that in sitting position at 3 minutes, that difference was not significant. CONCLUSIONS AND CLINICAL RELEVANCE: Body position affects IOP in dogs. When IOP is measured in dogs, body position should be recorded and consistent among repeat evaluations.     

Pharmacokinetics of carvedilol after intravenous and oral administration in conscious healthy dogs

OBJECTIVE: To determine the pharmacokinetics of carvedilol administered IV and orally and determine the dose of carvedilol required to maintain plasma concentrations associated with anticipated therapeutic efficacy when administered orally to dogs. ANIMALS: 8 healthy dogs. PROCEDURES: Blood samples were collected for 24 hours after single doses of carvedilol were administered IV (175 microg/kg) or PO (1.5 mg/kg) by use of a crossover nonrandomized design. Carvedilol concentrations were detected in plasma by use of high-performance liquid chromatography. Plasma drug concentration versus time curves were subjected to noncompartmental pharmacokinetic analysis. RESULTS: The median peak concentration (extrapolated) of carvedilol after IV administration was 476 ng/mL (range, 203 to 1,920 ng/mL), elimination half-life (t(1/2)) was 282 minutes (range, 19 to 1,021 minutes), and mean residence time (MRT) was 360 minutes (range, 19 to 819 minutes). Volume of distribution at steady state was 2.0 L/kg (range, 0.7 to 4.3 L/kg). After oral administration of carvedilol, the median peak concentration was 24 microg/mL (range, 9 to 173 microg/mL), time to maximum concentration was 90 minutes (range, 60 to 180 minutes), t(1/2) was 82 minutes (range, 64 to 138 minutes), and MRT was 182 minutes (range, 112 to 254 minutes). Median bioavailability after oral administration of carvedilol was 2.1% (range, 0.4% to 54%). CONCLUSIONS AND CLINICAL RELEVANCE: Although results suggested a 3-hour dosing interval on the basis of MRT, pharmacodynamic studies investigating the duration of beta-adrenoreceptor blockade provide a more accurate basis for determining the dosing interval of carvedilol.     

Serum cardiac troponin I and cardiac troponin T concentrations in dogs with gastric dilatation-volvulus

OBJECTIVE: To determine whether serum concentrations of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) are increased in dogs with gastric dilatationvolvulus (GDV) and whether concentrations correlate with severity of ECG abnormalities or outcome. DESIGN: Prospective case series. ANIMALS: 85 dogs with GDV. PROCEDURE: Serum cTnl and cTnT concentrations were measured 12 to 24, 48, 72, and 96 hours after surgery. Dogs were grouped on the basis of severity of ECG abnormalities and outcome. RESULTS: cTnl and cTnT were detected in serum from 74 (87%) and 43 (51%) dogs, respectively. Concentrations were significantly different among groups when dogs were grouped on the basis of severity of ECG abnormalities (none or mild vs moderate vs severe). Dogs that died (n = 16) had significantly higher serum cTnI (24.9 ng/ml) and cTnT (0.18 ng/ml) concentrations than did dogs that survived (2.05 and < 0.01 ng/ml, respectively). Myocardial cell injury was confirmed at necropsy in 4 dogs with high serum cardiac troponin concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that concentrations of cTnI and cTnT suggestive of myocardial cell injury can commonly be found in serum from dogs with GDV and that serum cardiac troponin concentrations are associated with severity of ECG abnormalities and outcome.     

Ocular penetration of intravenously administered enrofloxacin in the horse

REASON FOR PERFORMING STUDY: Information on antibiotic concentrations in the equine eye following systemic therapy is limited. Reports that Leptospira spp. are frequently present in the eyes of horses with recurrent uveitis, emphasises a need for studies on ocular concentrations of specific antibiotics. HYPOTHESES: 1) Enrofloxacin, administered i.v. at 7.5 mg/kg bwt q. 24 h, results in aqueous humour concentrations greater than the reported minimum inhibitory concentration (MIC) for Leptospira pomona. 2) Aqueous humour paracentesis sufficiently disrupts the blood-aqueous humour barrier (BAB) to cause an increase in aqueous humour protein and enrofloxacin concentrations. METHODS: Aqueous humour enrofloxacin and total protein concentrations were determined in 6 healthy, mature horses after i.v. administration of enrofloxacin. Paracentesis was performed on the left eye on Days 3 and 4, 1 h following enrofloxacin administration, to determine enrofloxacin concentrations in healthy eyes and in eyes with mechanical disruption of the BAB. Paracentesis was also performed on the right eye 23 h after enrofloxacin administration. Blood samples were collected from the horses at identical times to determine enrofloxacin aqueous humour:plasma ratios. RESULTS: Mean +/- s.d. enrofloxacin concentration in the aqueous humour 1 h post administration on Day 3 was 0.32 +/- 0.10 mg/l (range 0.18-0.47); and aqueous humour enrofloxacin, total protein and aqueous humour:plasma enrofloxacin ratios were higher on Day 4 than Day 3. CONCLUSIONS AND POTENTIAL RELEVANCE: Following disruption of the BAB, enrofloxacin concentrations were above the reported MIC for Leptospira pomona.