Estimation of the probability for exceeding a threshold concentration of furosemide at various intervals after intravenous administration in horses

OBJECTIVE: To estimate the probability for exceeding a threshold concentration of furosemide commonly used for regulatory purposes after IV administration of furosemide in horses. ANIMALS: 12 mature healthy horses (6 Thoroughbreds and 6 Quarter Horses). PROCEDURE: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after administration of 250 or 500 mg of furosemide. Concentrations of furosemide were determined, using an ELISA. Concentration of furosemide was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic data, the probability for exceeding a concentration of 100 ng/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess inherent variation in this estimated probability. RESULTS: The estimated probability of exceeding the threshold of 100 ng of furosemide/ml ranged from 11.6% at 4 hours to 2.2% at 5.5 hours after IV administration of 250 mg of furosemide/horse and 34.2% at 4 hours to 12.3% at 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identified in violation of regulatory concentrations was inversely associated with time and positively associated with dose. CONCLUSIONS AND CLINICAL RELEVANCE: Interhorse variability with respect to pharmacokinetics of furosemide will result in misclassification of some horses as being in violation of regulatory concentrations.     

Systemic progesterone concentration following human chorionic gonadotropin administration at various times during the estrous cycle in beef heifers

In Trial 1, 26 heifers were allotted randomly to a control group or one of four groups to receive a single injection of 3,000 IU hCG on d 1, 4, 7 or 10 of an estrous cycle. Heifers next completed a nontreated cycle, and at their third estrus were reallotted to one of the five groups described previously. Estrous cycle length was extended in cycle 1 but was not altered during the nontreated cycle or in cycle 3. Administration of hCG on d 4 or 7 increased (P less than .05) mean serum progesterone (P4) over the first 16 d of the estrous cycle by .9 and .8 ng/ml, respectively. In Trial 2, 23 heifers were allotted randomly to one of two groups to receive a placebo or a single injection of 3,000 IU hCG on d 4 of an estrous cycle. Heifers were inseminated artificially at subsequent estrus. On d 4 postbreeding, treatments were repeated. Administration of hCG on d 4 of the prebreeding estrous cycle increased (P less than .05) mean P4 over the first 16 d by .9 ng/ml, whereas mean P4 over the first 16 d postbreeding was not affected by a second injection of hCG on d 4 postbreeding. Administration of hCG increased (P less than .05) first-service pregnancy rate (92 vs 55%). In conclusion, progesterone concentrations were enhanced by hCG given on d 4 or 7 of the estrous cycle, and pregnancy rate was increased when hCG was administered both on d 4 of the prebreeding cycle and d 4 postmating.     

C-reactive protein concentration in dogs with various diseases

To investigate the clinical utility of C-reactive protein (CRP) determination in dogs, its plasma concentration was measured by a laser nephelometric method in 928 dogs with various diseases, and was compared with other inflammatory parameters. CRP concentration was elevated in various inflammatory diseases, this was most frequently observed in cases with neoplastic and immune-mediated diseases. All cases of pyometra, panniculitis, acute pancreatitis, polyarthritis, and hemangiosarcoma showed significantly elevated CRP concentrations. On the other hand, the CRP concentration was elevated only in few cases of neurological diseases such as epilepsy, meningoencephalitis, and hydrocephalus and endocrine diseases such as hypothyroidism, hyperadrenocorticism, and diabetes mellitus. Only a weak correlation was observed between the CRP concentration and white blood cell (WBC) counts (r=0.44) but no correlation with band neutrophil counts. There was no correlation between the CRP and albumin concentrations, but a weak negative correlation (r=-0.40) when excluding chronic intestinal diseases and nephrotic syndrome, which can cause protein loss. Thus, CRP can be useful to detect inflammations that cannot be detected by WBC and, or band neutrophil counts, suggesting that the examination of CRP concentration is essential as routine diagnostic test.     

A comparison of the various routes of administration of erythromycin in cattle

A comparison of i.v., i.m. and s.c. administration erythromycin base in polyethylene glycol at 15 mg/kg and 30 mg/kg body weight was carried out in beef-type calves of approximately 200 kg body weight. Additional evaluations were carried out with oral administration of erythromycin phosphate and erythromycin stearate. Absorption of erythromycin was very slow by both the i.m. and s.c. routes of administration with a K_ab of 0.0135 min^-1 and 0.0185 min^-1 for i.m. and 0.0032 min^-1 and 0.0074 min^-1 for s.c. at 15 mg/kg and 30 mg/kg, respectively. The bioavailability (32–42%) and peak serum concentrations were much lower with s.c. than with i.m. (60–65%) administration. The disposition of erythromycin administered i.v. appeared to be representative of dose-dependent kinetics rather than dose-independent first-order kinetics inasmuch as the elimination half-time ( t _1/2B) increased from 174.5 ± 13 min for the 15 mg/kg dosage to 239 ± 10.8 min with 30 mg/kg dosage. An acute apparent cardiovascular effect accompanied i.v. administration of erythromycin at 30 mg/kg dosage but not at 15 mg/kg. Severe diarrhea followed oral administration of either erythromycin phosphate or erythromycin stearate.     

Superovulation after administration of PMSG in cows of various breeds

Superovulation response was studied to i. m. administration of 2500 and 3000 i. u. of PMSG (special product Folligon, Intervet Co.) in 67 breeding cows of the Black-Pied Lowland. Slovak Pied and Slovak Pinzgau breeds within the 9th to 12th days of their sexual cycles. The time which had elapsed from these cows' last calving ranged from 50 to 150 days and the number of their prior calvings ranged from one to ten. The best superovulation effect was obtained after the administration of 2500 i. u. PMSG in the Pinzgau breed: these cows had, on the average, 13.20 +/- 2.36 corpora lutea without non-ovulated follicles. At the PMSG dose increased to 3000 i. u., the number of yellow bodies rose to 18.11 +/- 1.12 and that of non-ovulated follicles to 3.46 +/- 0.46. In the Slovak Pied breed the average number of yellow bodies obtained after administration of 2500 i. u. PMSG was 11.74 +/- 1.27 and that of non-ovulated follicles was 0.44 +/- 0.02. At the PMSG dose of 3000 i. u., the number of yellow bodies increased to 15.49 +/- 1.62 and that of non-ovulated follicles increased up to 5.12 +/- 0.81. In the Black-Pied Lowland breed the lowest response was obtained: the i. m. administration of 2500 i. u. PMSG resulted in the formation of 9.5 +/- 0.84 yellow bodies and 1.16 +/- 0.26 non-ovulated follicles, and at the dose of 3000 i. u. the respective numbers were 13.41 +/- 0.89 and 3.07 +/- 0.39. Comparing the superovulation effect in dependence on age, the response of the cows of the Black-Pied Lowland and Slovak Pinzgau breeds to PMSG administration increases until the age of nine years (from 9.79 and 13.6 yellow bodies, respectively, on the average for the first five years to 12.71 and 17.99, respectively, in the ninth year); in the Slovak Pinzgau breed it decreases from 15.83, recorded in the first five years, to 8.28 +/- 1.68 in the ninth year. The number of non-ovulated follicles grows with age in the Slovak Pinzgau breed from 3.46 +/- 0.46 in the first five years to 3.64 between five and nine years of age and up to 4.44 +/- 0.52 after the ninth year, in the Slovak Pied breed from 0.79 to 4.21 +/- 0.38, and in the Black-Pied Lowland breed from 2.69 to 3.20 +/- 0.22 between the fifth and ninth year.     

Estimation of the probability for exceeding thresholds of urine specific gravity and plasma concentration of furosemide at various intervals after intravenous administration of furosemide in horses

OBJECTIVE: To estimate the probability of concurrently exceeding thresholds for plasma concentration of furosemide and urine specific gravity after IV administration of furosemide in horses. ANIMALS: 12 mature healthy Thoroughbred (n = 6) or Quarter Horse (6) mares. PROCEDURE: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after IV administration of 250 mg (first experiment) or 500 mg (second experiment) of furosemide. Urine was collected hourly between 1 and 6 hours after administration of furosemide at both doses. Concentrations of furosemide were determined by use of an ELISA. Concentration of furosemide and urine specific gravity was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic and specific gravity data, the probability of exceeding a concentration of 100 ng of furosemide/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess the inherent variation in this estimated probability. RESULTS: The estimated probability of exceeding the threshold of 100 ng of furosemide/ml and urine specific gravity < 1.012 was approximately 0% between 4.0 and 5.5 hours after IV administration of 250 mg of furosemide/horse, and ranged from 0 to 1% between 4 and 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identified as in violation of regulatory concentrations was inversely associated with time. CONCLUSIONS AND CLINICAL RELEVANCE: Coupling plasma furosemide concentration with urine specific gravity testing will greatly reduce the chance that some horses are misclassified as being in violation of regulatory concentrations.     

Effect of chorionic gonadotropin administration on the concentration of testosterone in the blood of boars]

In intact boars, intravenous administration of 100 to 6000 I. U. chorionic gonadotropin elicited a pronounced rise in the plasma level of testosterone, depending on the time interval from the administration of chorionic gonadotropin and on the size of the administered dose. In the blood of castrated boars such an application of choronic gonadotropin did not influence the concentration of testosterone. It was inferred that the rise in the levels of blood testosterone in boars after administration of chorionic gonadotropin was specific for testicular incretion and indicated the endocrine reserve of the testes. There is a discussion concerning the importance of the functional testing of the incretion capacity of testes for differential diagnosis different forms o incretion hypogonadism.     

Effects of epidural administration of dexmedetomidine on the minimum alveolar concentration of isoflurane in dogs

Objective-To evaluate the effects of epidural administration of 3 doses of dexmedetomidine on isoflurane minimum alveolar concentration (MAC) and characterize changes in bispectral index (BIS) induced by nociceptive stimulation used for MAC determination in dogs. Animals-6 adult dogs. Procedures-Isoflurane-anesthetized dogs received physiologic saline (0.9% NaCl) solution (control treatment) or dexmedetomidine (1.5 [DEX1.5], 3.0 [DEX3], or 6.0 [DEX6] mug/kg) epidurally in a crossover study. Isoflurane MAC (determined by use of electrical nociceptive stimulation of the hind limb) was targeted to be accomplished at 2 and 4.5 hours. Changes in BIS attributable to nociceptive stimulation and cardiopulmonary data were recorded at each MAC determination. Results-With the control treatment, mean +/- SD MAC values did not change over time (1.57 +/- 0.23% and 1.55 +/- 0.25% at 2 and 4.5 hours, respectively). Compared with the control treatment, MAC was significantly lower at 2 hours (13% reduction) but not at 4.5 hours (7% reduction) in DEX1.5-treated dogs and significantly lower at 2 hours (29% reduction) and 4.5 hours (13% reduction) in DEX3-treated dogs. The DEX6 treatment yielded the greatest MAC reduction (31% and 22% at 2 and 4.5 hours, respectively). During all treatments, noxious stimulation increased BIS; but changes in BIS were correlated with increases in electromyographic activity. Conclusions and Clinical Relevance-In dogs, epidural administration of dexmedetomidine resulted in dose-dependent decreases in isoflurane MAC and that effect decreased over time. Changes in BIS during MAC determinations may not represent increased awareness because of the possible interference of electromyographic activity.     

Vitamin E serum levels in calves after various methods of administration]

We observed the levels of vitamin E in the blood serum of calves after peroral application of Combinal E (1 ml contains 20 mg of tocopherol acetate in water solution), after application through a fistula into the rennet stomach and after an intramuscular injection of Erevit (1 ml contains 300 mg of tocopherol acetate in vegetable oil). The fastest increase in the vitamin E level was recorded after the application of Combinal E directly into the rennet stomach. The application of Combinal E per os resulted in the same level of vitamin E in the ninth hour after application as in the third hour after application into the rennet stomach, the intramuscular injection of Erevit had a much lower effect on raising the vitamin E level in the blood serum of calves. It was confirmed that for a faster supplementing of vitamin E to the organism it is more suitable to give Combinal E perorally.