Passive transfer of maternal immunoglobulin isotype antibodies against tetanus and influenza and their effect on the response of foals to vaccination.

Influenza and tetanus-specific antibodies of the IgG sub-isotypes are posively transferred to foals via colostrum and inhibit their response to inactivated influenza vaccines and tetanus toxoid. High titres of influenza antibodies of IgGa and IgGb subisotypes and tetanus antibodies of the IgGa, IgGb and IgG(T) subisotypes were detected in postsucking serum samples collected from foals born to mares that had received booster doses of multicomponent vaccines during the last 2 months of gestation. Thereafter, titres declined in an exponential manner but were still detectable in all foals at age 26 weeks, regardless of whether they had been vaccinated prior to age 26 weeks. Mean +/- s.e. half-life of decline of influenza IgGa antibodies (27.0 +/- 2.3 days) was significantly shorter than that of influenza IgGb antibodies (39.1 +/- 2.7 days; P<0.005). Tetanus IgGa and IgGb antibodies declined with half-lives of 28.8 +/- 3.0 and 34.8 +/- 5.1 days, respectively. Titres of tetanus IgG(T) antibodies were substantially higher than those of influenza IgG(T) antibodies in postsucking samples and remained so through age 26 weeks, declining with a half-life of approximately 35 days. Postsucking titres of tetanus and influenza antibodies of the IgA isotype were low and declined rapidly to undetectable levels. Yearlings showed significant increases in titre of influenza IgGa, IgGb and IgG(T) subisotype antibodies but no increase in influenza IgA antibodies in response to 2 doses of multicomponent vaccines containing tetanus toxoid and inactivated influenza A-1 and A-2 antigens. Yearlings also showed strong tetanus IgGa, IgGb and IgG(T) subisotype responses to one dose of vaccine and a substantial further rise in titre in response to administration of a second dose 3 weeks later, but failed to show an increase in titre of tetanus IgA antibodies. The influenza and tetanus IgGa, IgGb and IgG(T) subisotype responses of 6-month-old foals to vaccination followed the same pattern as those shown by yearlings but titres were generally lower. In contrast, 3-month-old foals failed to show increases in titre of either influenza or tetanus IgG subisotypes in response to 2 doses of vaccine and generally needed 1-3 additional booster doses of vaccine to achieve titres similar to those achieved by yearlings after 2 doses. Based on the finding that maternal antibodies exert a significant inhibitory effect on the response of foals to tetanus toxoid and inactivated influenza antigens, it is recommended that primary immunisation of foals born to vaccinated mares should not commence before age 6 months.

Effects of prior feeding on pharmacokinetics and estimated bioavailability after oral administration of a single dose of microencapsulated erythromycin base in healthy foals.

OBJECTIVE: To determine effects of prior feeding on pharmacokinetics and estimated bioavailability of orally administered microencapsulated erythromycin base (MEB) in healthy foals. ANIMALS: 6 healthy foals, 3 to 5 months old. PROCEDURE: Foals were given 2 doses of MEB (25 mg/kg of body weight, PO). One dose was administered after food was withheld overnight, and the other was administered after foals had consumed hay. The study used a crossover design with a 2-week period between doses. Blood was collected via a jugular vein prior to and at specific times after drug administration. Concentrations of erythromycin A and anhydroerythromycin A in plasma were determined, using high-performance liquid chromatography. Results pharmacokinetic analysis of plasma concentration-time data for food-withheld and fed conditions were compared. RESULTS: Plasma concentrations of erythromycin A for foals were lower after feeding than concentrations when food was withheld. Area under the plasma concentration-time curve, maximum plasma concentration, and estimated bioavailability were greater in foals when food was withheld than when foals were fed. Anhydroerythromycin A was detected in plasma after administration of MEB in all foals. CONCLUSIONS AND CLINICAL RELEVANCE: Foals should be given MEB before they are fed hay. Administration of MEB to foals from which food was withheld overnight apparently provides plasma concentrations of erythromycin A that exceed the minimum inhibitory concentration of Rhodococcus equi for approximately 5 hours. The dosage of 25 mg/kg every 8 hours, PO, appears appropriate.

Pharmacokinetics of erythromycin estolate and erythromycin phosphate after intragastric administration to healthy foals.

OBJECTIVE: To determine pharmacokinetics and plasma concentrations of erythromycin and related compounds after intragastric administration of erythromycin phosphate and erythromycin estolate to healthy foals. ANIMALS: 11 healthy 2- to 6-month-old foals. PROCEDURE: Food was withheld from foals overnight before intragastric administration of erythromycin estolate (25 mg/kg of body weight; n = 8) and erythromycin phosphate (25 mg/kg; 7). Four foals received both drugs with 2 weeks between treatments. Plasma erythromycin concentrations were determined at various times after drug administration by use of high-performance liquid chromatography. Maximum plasma peak concentrations, time to maximum concentrations, area under plasma concentration versus time curves, half-life of elimination, and mean residence times were determined from concentration versus time curves. RESULTS: Maximum peak concentration of erythromycin A after administration of erythromycin phosphate was significantly greater than after administration of erythromycin estolate (2.9 +/- 1.1 microg/ml vs 1.0 +/- 0.82 microg/ml). Time to maximum concentration was shorter after administration of erythromycin phosphate than after erythromycin estolate (0.71 +/- 0.29 hours vs 1.7 +/- 1.2 hours). Concentrations of anhydroerythromycin A were significantly less 1 and 3 hours after administration of erythromycin estolate than after administration of erythromycin phosphate. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma concentrations of erythromycin A remained > 0.25 microg/ml (reported minimum inhibitory concentration for Rhodococcus equi) for at least 4 hours after intragastric administration of erythromycin phosphate or erythromycin estolate, suggesting that the recommended dosage for either formulation (25 mg/kg, q 6 h) should be adequate for treatment of R equi infections in foals.

Efficacy of florfenicol for treatment of naturally occurring infectious bovine keratoconjunctivitis.

OBJECTIVE: To determine the efficacy of florfenicol for treatment of calves with naturally occurring infectious bovine keratoconjunctivitis (IBK). DESIGN: Randomized controlled field trial. ANIMALS: 63 beef calves and 80 dairy calves between 4 and 12 months of age. PROCEDURE: Calves were randomly assigned to 1 of 3 treatment groups. Calves in the SC treatment group received a single dose of florfenicol (40 mg/kg [18.2 mg/lb of body weight), SC, on day 0. Calves in the IM treatment group received florfenicol (20 mg/kg [9.1 mg/lb]), IM, on days 0 and 2. Calves in the control group received injections of saline solution (0.9% NaCl), IM, on days 0 and 2. Calves were reevaluated every other day for 20 days after treatment. RESULTS: Corneal ulcers healed by day 20 in 48 of 49 (98%) calves treated with florfenicol IM, 39 of 42 (93%) calves treated with florfenicol SC, and 33 of 52 (63%) control calves. CONCLUSIONS AND CLINICAL RELEVANCE: Florfenicol administered SC (1 dose) or IM (2 doses 48 hours apart) was effective for treatment of calves with naturally occurring IBK.

Comparison of microbiologic and high-performance liquid chromatography assays to determine plasma concentrations, pharmacokinetics, and bioavailability of erythromycin base in plasma of foals after intravenous or intragastric administration.

OBJECTIVE: To determine pharmacokinetics and bioavailability of erythromycin base after intragastric administration and erythromycin lactobionate after IV administration to healthy foals and to compare a microbiologic assay with a high-performance liquid chromatography (HPLC) method to determine plasma concentrations of erythromycin A. ANIMALS: 6 healthy foals that were 2 to 4 months old. PROCEDURE: Foals were given single doses of erythromycin (10 mg/kg of body weight, IV, and 25 mg/kg, intragastrically) in a crossover study. Venous blood samples were obtained at specific times after drug administration, and plasma was harvested for determination of erythromycin concentrations by microbiologic assay and a HPLC method Pharmacokinetic analysis of plasma concentration-time data was performed, and results derived from each method were compared. RESULTS: Concentration-time profiles for IV administration were best described by a two-compartment open model. Comparing pharmacokinetic data obtained by the 2 methods revealed substantial differences in results. Values for area under the plasma concentration-time curve and area under the first moment of the curve were substantially higher when determined by the bioassay, indicating overestimation of plasma concentration-time data by this method. The derived rate transfer constants (K21 and K(e)1) and mean residence time were significantly different, when determined by the bioassay. Systemic bioavailability of erythromycin base was low in all foals. CONCLUSIONS AND CLINICAL RELEVANCE: The bioassay method overestimated plasma concentrations of erythromycin, compared with the HPLC method. Despite low systemic bioavailability of erythromycin base administered intragastrically, plasma concentrations of erythromycin exceeded, for at least 4 hours, the minimum inhibitory concentration of most Rhodococcus equi isolates.

Effect of route of administration and age on the pharmacokinetics of amikacin administered by the intravenous and intraosseous routes to 3 and 5-day-old foals.

The suitability of the intraosseous (i.o.) route for drug administration to equine neonates was evaluated in a study comparing the pharmacokinetics of amikacin administered by the i.o. and intravenous (i.v.) routes. Using a cross-over study design amikacin sulphate (7 mg/kg bwt) was administered i.o. or i.v. to 6 healthy foals at 3 and 5 days of age. Amikacin was instantaneously and completely absorbed after i.o. administration, achieving a mean +/- sd peak concentration (34.17 +/- 3.54 micrograms/ml) in the first sample collected 3 min after administration which was not significantly different from the mean +/- sd peak concentration (32.92 +/- 2.63 micrograms/ml) achieved after i.v. administration. The plasma amikacin concentration-time profiles for the i.o. and i.v. routes were not different and both were appropriately described by a 2-compartment open pharmacokinetic model. No significant differences attributable to route of administration were found in values for the major pharmacokinetic variables. The degree of inter-individual variation in values for indices of clearance was considerably greater than the degree of variation attributable to age. Despite this, values for body clearance (ClB) were significantly higher (P < 0.05) and values for area under the plasma amikacin concentration-time curve (AUC) and concentration of amikacin in plasma at 8 h [Cp(8h)] were significantly lower in 5- than in 3-day-old foals, indicating that amikacin was more rapidly cleared by the older foals. Technical difficulties were not encountered during i.o. needle placement in the medial aspect of the proximal tibia. Mild diffuse soft tissue swelling which developed at the i.o. site resolved completely within 1-2 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of age on the disposition kinetics of chloramphenicol in equine neonates.

The effect of age on the pharmacokinetics of chloramphenicol was determined after IV administration of chloramphenicol sodium succinate (25 mg/kg of body weight) to 6 foals at 1 day and 3, 7, 14, and 42 days of age. The disposition of chloramphenicol was best described, using a two-compartment open model in all foals at all ages evaluated. Significant age-related changes were observed in values for the major kinetic terms describing the disposition of chloramphenicol in foals; the greatest changes were observed between 1 day and 3 days of age. The mean +/- SD value for elimination rate constant (beta) for chloramphenicol in 1-day-old foals (0.131 +/- 0.06 h-1) was significantly (P less than 0.005) lower than the value in 3-day-old foals (0.514 +/- 0.156 h-1), and both values were significantly (P less than 0.05) lower than values for beta in 7-, 14-, and 42-day-old foals. With increasing age, the increase in the mean value for beta resulted in decrease in the harmonic mean elimination half-time (t1/2 beta) for chloramphenicol, from 5.29 hours in 1-day-old foals to: 1.35 hours in 3-day-old foals; 0.61 hour in 7-day-old foals; 0.51 hour in 14-day-old foals; and 0.34 hour in 42-day-old foals. At 1, 3, and 7 days of age, values for t1/2 beta of chloramphenicol in a premature foal born after parturition was induced with oxytocin, were considerably longer than comparable t1/2 beta values for term foals born naturally.(ABSTRACT TRUNCATED AT 250 WORDS)

Ormetoprim-sulfadimethoxine in cattle: pharmacokinetics, bioavailability, distribution to the tears, and in vitro activity against Moraxella bovis.

The pharmacokinetics, bioavailability, and distribution to the tears of ormetoprim (OMP; 5.5 mg/kg of body weight) and sulfadimethoxine (SDM; 27.5 mg/kg of body weight) were determined following IV or oral administration to 6 Holstein steers. After IV administration, the disposition kinetics of both drugs were best described by a 2-compartment open model. Sulfadimethoxine had a moderately rapid distribution phase, followed by a slower elimination phase, with a mean half-life (t 1/2) of 7.91 hours. The mean volume of distribution of SDM was 185 ml/kg, and the mean body clearance was 0.28 ml/min X kg. The concentration of SDM in tears was lower than the corresponding plasma concentration, and the elimination of SDM from tears (t 1/2 = 3.02 hours) was significantly faster than its elimination from plasma (t 1/2 = 7.91 hours). The disposition of OMP administered IV was characterized by a rapid distribution phase, followed by a rapid elimination phase (t 1/2 = 1.37 hours). The high values of the mean volume of distribution (1,450 ml/kg) and mean rate of body clearance (13.71 ml/min X kg) indicated that OMP was widely distributed in the body and was rapidly cleared from the body. Ormetoprim concentrations in tears exceeded corresponding plasma concentrations, and the elimination of OMP from tears was significantly slower (t 1/2 = 1.91 hours) than from plasma (t 1/2 = 1.37 hours). After oral administration of an OMP-SDM combination in bolus form, the absorption of SDM was slow (absorption t 1/2 = 3.32 hours), but complete.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics and endometrial tissue concentrations of ticarcillin given to the horse by intravenous and intrauterine routes.

Plasma and endometrial tissue concentrations of ticarcillin were measured in healthy mares. In the first of the 3 separate phases comprising the study, ticarcillin disodium (30 mg/kg) was administered IV. The mean peak concentration in endometrial tissue, 12.9 micrograms/g, was attained at 30 minutes. The plasma half-life of the drug in the 6 mares was 0.83 +/- 0.22 hour. Six grams of the drug was diluted in 250 ml of sodium chloride injection USP (2nd phase) and in 60 ml of sodium chloride injection USP (3rd phase). These dilutions were administered by intrauterine infusion. In phase 2, the mean peak concentrations of the drug in plasma and endometrium were 2.76 micrograms/ml and greater than 150 micrograms/g, respectively, at 60 minutes after it was administered. Endometrial concentrations greater than 150 micrograms of ticarcillin/g persisted through 2 hours after the drug was administered. Mean peak plasma and endometrial concentrations of the drug in phase 3 were 2.78 micrograms/ml and greater than 150 micrograms/g at 45 and 30 minutes after administration was done, respectively. At 1 hour after the drug was administered, endometrial concentrations of ticarcillin were significantly higher (P less than 0.01) after the drug was infused intrauterinely in the 250-ml volume than those after the 60-ml volume was infused. It was concluded that the volume of fluid in which the drug was infused into the uterus markedly influenced the duration of concentrations greater than 20 micrograms/g in endometrial tissue.