Objective—To determine pharmacokinetics of clarithromycin and concentrations in body fluids and bronchoalveolar (BAL) cells of foals.
Animals—6 healthy 2-to 3-week-old foals.
Procedures—In a crossover design, clarithromycin (7.5 mg/kg) was administered to each foal via IV and intragastric (IG) routes. After the initial IG administration, 5 additional doses were administered IG at 12-hour intervals. Concentrations of clarithromycin and its 14-hydroxy metabolite were measured in serum by use of high-performance liquid chromatography. A microbiologic assay was used to measure clarithromycin activity in serum, urine, peritoneal fluid, synovial fluid, CSF, pulmonary epithelial lining fluid (PELF), and BAL cells.
Results—After IV administration, elimination half-life (5.4 hours) and mean ± SD body clearance (1.27 ± 0.25 L/h/kg) and apparent volume of distribution at steady state (10.4 ± 2.1 L/kg) were determined for clarithromycin. The metabolite was detected in all 6 foals by 1 hour after clarithromycin administration. Oral bioavailability of clarithromycin was 57.3 ± 12.0%. Maximum serum concentration of clarithromycin after multiple IG administrations was 0.88 ± 0.19 μg/mL. After IG administration of multiple doses, clarithromycin concentrations in peritoneal fluid, CSF, and synovial fluid were similar to or lower than concentrations in serum, whereas concentrations in urine, PELF, and BAL cells were significantly higher than concentrations in serum.
Conclusions and Clinical Relevance—Oral administration of clarithromycin at 7.5 mg/kg every 12 hours maintains concentrations in serum, PELF, and BAL cells that are higher than the minimum inhibitory concentration (0.12 μg/mL) for Rhodococcus equiisolates for the entire 12-hour dosing interval.
Objective—To determine the effects of dobutamine, norepinephrine, and vasopressin on cardiovascular function and gastric mucosal perfusion in anesthetized foals during isoflurane-induced hypotension.
Animals—6 foals that were 1 to 5 days of age.
Procedures—6 foals received 3 vasoactive drugs with at least 24 hours between treatments. Treatments consisted of dobutamine (4 and 8 μg/kg/min), norepinephrine (0.3 and 1.0 μg/kg/min), and vasopressin (0.3 and 1.0 mU/kg/min) administered IV. Foals were maintained at a steady hypotensive state induced by a deep level of isoflurane anesthesia for 30 minutes, and baseline cardiorespiratory variables were recorded. Vasoactive drugs were administered at the low infusion rate for 15 minutes, and cardiorespiratory variables were recorded. Drugs were then administered at the high infusion rate for 15 minutes, and cardiorespiratory variables were recorded a third time. Gastric mucosal perfusion was measured by tonometry at the same time points.
Results—Dobutamine and norepinephrine administration improved cardiac index. Vascular resistance was increased by norepinephrine and vasopressin administration but decreased by dobutamine at the high infusion rate. Blood pressure was increased by all treatments but was significantly higher during the high infusion rate of norepinephrine. Oxygen delivery was significantly increased by norepinephrine and dobutamine administration; O2 consumption decreased with dobutamine. The O2 extraction ratio was decreased following norepinephrine and dobutamine treatments. The gastric to arterial CO2gap was significantly increased during administration of vasopressin at the high infusion rate.
Conclusion and Clinical Relevance—Norepinephrine and dobutamine are better alternatives than vasopressin for restoring cardiovascular function and maintaining splanchnic circulation during isofluraneinduced hypotension in neonatal foals.
Objective—To compare cardiac output (CO) measured by use of the partial carbon dioxide rebreathing method (NICO) or lithium dilution method (LiDCO) in anesthetized foals.
Sample Population—Data reported in 2 other studies for 18 neonatal foals that weighed 32 to 61 kg.
Procedures—Foals were anesthetized and instrumented to measure direct blood pressure, heart rate, arterial blood gases, end-tidal isoflurane and carbon dioxide concentrations, and CO. Various COs were achieved by administration of dobutamine, norepinephrine, vasopressin, phenylephrine, and isoflurane to allow comparisons between LiDCO and NICO methods. Measurements were obtained in duplicate or triplicate. We allowed 2 minutes between measurements for LiDCO and 3 minutes for NICO after achieving a stable hemodynamic plane for at least 10 to 15 minutes at each CO.
Results—217 comparisons were made. Correlation (r = 0.77) was good between the 2 methods for all determinations. Mean ± SD measurements of cardiac index for all comparisons with the LiDCO and NICO methods were 138 ± 62 mL/kg/min (range, 40 to 381 mL/kg/min) and 154 ± 55 mL/kg/min (range, 54 to 358 mL/kg/min), respectively. Mean difference (bias) between LiDCO and NICO measurements was −17.3 mL/kg/min with a precision (1.96 × SD) of 114 mL/kg/min (range, −131.3 to 96.7). Mean of the differences of LiDCO and NICO measurements was 4.37 + (0.87 × NICO value).
Conclusions and Clinical Relevance—The NICO method is a viable, noninvasive method for determination of CO in neonatal foals with normal respiratory function. It compares well with the more invasive LiDCO method.
OBJECTIVE To determine pharmacokinetics and pulmonary disposition of minocycline in horses after IV and intragastric administration.
ANIMALS 7 healthy adult horses.
PROCEDURES For experiment 1 of the study, minocycline was administered IV (2.2 mg/kg) or intragastrically (4 mg/kg) to 6 horses by use of a randomized crossover design. Plasma samples were obtained before and 16 times within 36 hours after minocycline administration. Bronchoalveolar lavage (BAL) was performed 4 times within 24 hours after minocycline administration for collection of pulmonary epithelial lining fluid (PELF) and BAL cells. For experiment 2, minocycline was administered intragastrically (4 mg/kg, q 12 h, for 5 doses) to 6 horses. Plasma samples were obtained before and 20 times within 96 hours after minocycline administration. A BAL was performed 6 times within 72 hours after minocycline administration for collection of PELF samples and BAL cells.
RESULTS Mean bioavailability of minocycline was 48% (range, 35% to 75%). At steady state, mean ± SD maximum concentration (Cmax) of minocycline in plasma was 2.3 ± 1.3 μg/mL, and terminal half-life was 11.8 ± 0.5 hours. Median time to Cmax (Tmax) was 1.3 hours (interquartile range [IQR], 1.0 to 1.5 hours). The Cmax and Tmax of minocycline in the PELF were 10.5 ± 12.8 μg/mL and 9.0 hours (IQR, 5.5 to 12.0 hours), respectively. The Cmax and Tmax for BAL cells were 0.24 ± 0.1 μg/mL and 6.0 hours (IQR, 0 to 6.0 hours), respectively.
CONCLUSIONS AND CLINICAL RELEVANCE Minocycline was distributed into the PELF and BAL cells of adult horses.
OBJECTIVE To determine the effects of oral omeprazole administration on the fecal and gastric microbiota of healthy adult horses.
ANIMALS 12 healthy adult research horses.
PROCEDURES Horses were randomly assigned to receive omeprazole paste (4 mg/kg, PO, q 24 h) or a sham (control) treatment (tap water [20 mL, PO, q 24 h]) for 28 days. Fecal and gastric fluid samples were collected prior to the first treatment (day 0), and on days 7, 28, 35, and 56. Sample DNA was extracted, and bacterial 16S rRNA gene sequences were amplified and sequenced to characterize α and β diversity and differential expression of the fecal and gastric microbiota. Data were analyzed by visual examination and by statistical methods.
RESULTS Composition and diversity of the fecal microbiota did not differ significantly between treatment groups or over time. Substantial variation in gastric fluid results within groups and over time precluded meaningful interpretation of the microbiota in those samples.
CONCLUSIONS AND CLINICAL RELEVANCE Results supported that omeprazole administration had no effect on fecal microbiota composition and diversity in this group of healthy adult horses. Small sample size limited power to detect a difference if one existed; however, qualitative graphic examination supported that any difference would likely have been small and of limited clinical importance. Adequate data to evaluate potential effects on the gastric microbiota were not obtained. Investigations are needed to determine the effects of omeprazole in horses with systemic disease or horses receiving other medical treatments.
Objective—To determine the disposition of gamithromycin in plasma, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and lung tissue homogenate in cattle.
Animals—33 healthy Angus calves approximately 7 to 8 months of age.
Procedures—Calves were randomly assigned to 1 of 11 groups consisting of 3 calves each, which differed with respect to sample collection times. In 10 groups, 1 dose of gamithromycin (6 mg/kg) was administered SC in the neck of each calf (0 hours). The remaining 3 calves were not treated. Gamithromycin concentrations in plasma, PELF, lung tissue homogenate, and BAL cells (matrix) were measured at various points by means of high-performance liquid chromatography with tandem mass spectrometry.
Results—Time to maximum gamithromycin concentration was achieved at 1 hour for plasma, 12 hours for lung tissue, and 24 hours for PELF and BAL cells. Maximum gamithromycin concentration was 27.8 μg/g, 17.8 μg/mL, 4.61 μg/mL, and 0.433 μg/mL in lung tissue, BAL cells, PELF, and plasma, respectively. Terminal half-life was longer in BAL cells (125.0 hours) than in lung tissue (93.0 hours), plasma (62.0 hours), and PELF (50.6 hours). The ratio of matrix to plasma concentrations ranged between 4.7 and 127 for PELF, 16 and 650 for lung tissue, and 3.2 and 2,135 for BAL cells.
Conclusions and Clinical Relevance—Gamithromycin was rapidly absorbed after SC administration. Potentially therapeutic concentrations were achieved in PELF, BAL cells, and lung tissue within 30 minutes after administration and persisted for 7 (PELF) to > 15 (BAL cells and lung tissue) days after administration of a single dose.
Objective—To determine the disposition of orally
administered cefpodoxime proxetil in foals and adult
horses and measure the minimum inhibitory concentrations
(MICs) of the drug against common bacterial
pathogens of horses.
Animals—6 healthy adult horses and 6 healthy foals
at 7 to 14 days of age and again at 3 to 4 months of
Procedure—A single dose of cefpodoxime proxetil
oral suspension was administered (10 mg/kg) to each
horse by use of a nasogastric tube. In 7- to 14-day-old
foals, 5 additional doses were administered intragastrically
at 12-hour intervals. The MIC of cefpodoxime
for each of 173 bacterial isolates was determined by
use of a commercially available test.
Results—In 7- to 14-day-old foals, mean ± SD time to
peak serum concentration (Tmax) was 1.7 ± 0.7 hours,
maximum serum concentration (Cmax) was 0.81 ±
0.22 µg/mL, and elimination half-life (harmonic mean)
was 7.2 hours. Disposition of cefpodoxime in 3- to 4-month-old foals was not significantly different from
that of neonates. Adult horses had significantly higher
Cmax and significantly lower Tmax, compared with
values for foals. The MIC of cefpodoxime required to
inhibit growth of 90% of isolates for Salmonella enterica,
Escherichia coli, Pasteurella spp, Klebsiella spp,
and β-hemolytic streptococci was 0.38, 1.00, 0.16,
0.19, and 0.09 µg/mL, respectively.
Conclusions and Clinical Relevance—Oral administration
at a dosage of 10 mg/kg every 6 to 12 hours
would appear appropriate for the treatment of equine
neonates with bacterial infections. (Am J Vet Res 2005;66:30–35)
Objective—To determine and compare the effects of caffeine and doxapram on cardiorespiratory variables in foals during isoflurane-induced respiratory acidosis.
Animals—6 clinically normal foals (1 to 3 days old).
Procedures—At intervals of ≥ 24 hours, foals received each of 3 IV treatments while in a steady state of hypercapnia induced by isoflurane anesthesia (mean ± SD, 1.4 ± 0.3% endtidal isoflurane concentration). After assessment of baseline cardiorespiratory variables, a low dose of the treatment was administered and variables were reassessed; a high dose was then administered, and variables were again assessed. Sequential low- and high-dose treatments included doxapram (loading dose of 0.5 mg/kg, followed by a 20-minute infusion at 0.03 mg/kg/min and then 0.08 mg/kg/min), caffeine (5 mg/kg and 10 mg/kg), and saline (0.9% NaCl) solution (equivalent volumes).
Results—Administration of doxapram at both infusion rates resulted in a significant increase in respiratory rate, minute ventilation, arterial blood pH, PaO2, and arterial blood pressure. These variables were also significantly higher during doxapram administration than during caffeine or saline solution administration. There was a significant dose-dependent decrease in PaCO2 and arterial bicarbonate concentration during doxapram treatment. In contrast, PaCO2 increased from baseline values after administration of saline solution or caffeine. The PaCO2 value was significantly lower during doxapram treatment than it was during caffeine or saline solution treatment.
Conclusions and Clinical Relevance—Results indicated that doxapram restored ventilation in a dose-dependent manner in neonatal foals with isoflurane-induced hypercapnia. The effects of caffeine on respiratory function were indistinguishable from those of saline solution.
Objective—To determine the pharmacokinetics of
azithromycin and its concentration in body fluids and
bronchoalveolar lavage cells in foals.
Animals—6 healthy 6- to 10-week-old foals.
Procedure—Azithromycin (10 mg/kg of body weight)
was administered to each foal via IV and intragastric
(IG) routes in a crossover design. After the first IG
dose, 4 additional IG doses were administered at 24-hour intervals. A microbiologic assay was used to
measure azithromycin concentrations in serum, peritoneal
fluid, synovial fluid, pulmonary epithelial lining
fluid (PELF), and bronchoalveolar (BAL) cells.
Results—Azithromycin elimination half-life was 20.3
hours, body clearance was 10.4 ml/min·kg, and apparent
volume of distribution at steady state was 18.6
L/kg. After IG administration, time to peak serum concentration
was 1.8 hours and bioavailability was 56%.
After repeated IG administration, peak serum concentration
was 0.63 ± 0.10 µg/ml. Peritoneal and synovial
fluid concentrations were similar to serum concentrations.
Bronchoalveolar cell and PELF concentrations
were 15- to 170-fold and 1- to 16-fold higher than concurrent
serum concentrations, respectively. No
adverse reactions were detected after repeated IG
Conclusions and Clinical Relevance—On the basis
of pharmacokinetic values, minimum inhibitory concentrations
of Rhodococcus equi isolates, and drug
concentrations in PELF and bronchoalveolar cells, a
single daily oral dose of 10 mg/kg may be appropriate
for treatment of R equi infections in foals. Persistence
of high azithromycin concentrations in PELF and bronchoalveolar
cells 48 hours after discontinuation of
administration suggests that after 5 daily doses, oral
administration at 48-hour intervals may be adequate.
(Am J Vet Res 2001;62:1870–1875)
Objective—To compare cardiac output (CO) measured by lithium arterial pressure waveform analysis (PULSECO) and CO measured by transpulmonary pulse contour analysis (PICCO) in anesthetized foals, with CO measured by use of lithium dilution (LIDCO) considered the criterion-referenced standard.
Sample Population—6 neonatal (1- to 4-day-old) foals that weighed 38 to 45 kg.
Procedures—Foals were anesthetized and instrumented to measure direct blood pressure, heart rate, arterial blood gases, and CO. The CO was measured by use of PULSECO, PICCO, and LIDCO techniques. Measurements were converted to specific CO (sCO) values for statistical analysis. Measurements were obtained during low, intermediate, and high CO states.
Results—sCO ranged from 75.5 to 310 mL/kg/min. Mean ± SD PICCO bias varied significantly among CO states and was −51.9 ± 23.1 mL/kg/min, 20.0 ± 19.5 mL/kg/min, and 87.2 ± 19.5 mL/kg/min at low, intermediate, and high CO states, respectively. Mean PULSECO bias (11.0 ± 37.5 mL/kg/min) was significantly lower than that of PICCO and did not vary among CO states. Concordance correlation coefficient between LIDCO and PULSECO was significantly greater than that between LIDCO and PICCO. The proportion of observations with a relative bias < ± 30% was significantly lower with the PULSECO method than with the PICCO method.
Conclusions and Clinical Relevance—Values for the PULSECO method were more reproducible and agreed better with values for the LIDCO method than did values for the PICCO method and were able to more accurately monitor changes in CO in anesthetized newborn foals.