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- Author or Editor: Lawrence R. Bernstein x
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Abstract
OBJECTIVE To determine serum and tissue concentrations of gallium (Ga) after oral administration of gallium nitrate (GaN) and gallium maltolate (GaM) to neonatal calves.
ANIMALS 8 healthy neonatal calves.
PROCEDURES Calves were assigned to 1 of 2 groups (4 calves/group). Gallium (50 mg/kg) was administered as GaN or GaM (equivalent to 13.15 mg of Ga/kg for GaN and 7.85 mg of Ga/kg for GaM) by oral gavage once daily for 5 days. Blood samples were collected 0, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after Ga administration on day 1; 4 and 24 hours after Ga administration on days 2, 3, and 4; and 4, 12, and 24 hours after Ga administration on day 5. On day 6, calves were euthanized and tissue samples were obtained. Serum and tissue Ga concentrations were measured by use of mass spectrometry.
RESULTS Data were adjusted for total Ga dose, and comparisons were made between the 2 groups. Calves receiving GaM had a significantly higher dose-adjusted area under the curve and dose-adjusted maximum serum Ga concentration than did calves receiving GaN. Despite receiving less Ga per dose, calves receiving GaM had tissue Ga concentrations similar to those for calves receiving GaN.
CONCLUSIONS AND CLINICAL RELEVANCE In this study, calves receiving GaM had significantly higher Ga absorption than did calves receiving GaN. These findings suggested that GaM might be useful as a prophylactic agent against Mycobacterium avium subsp paratuberculosis infection in neonatal calves. (Am J Vet Res 2016;77:151–155)
Abstract
Objective—To determine the pharmacokinetics of gallium maltolate (GaM) after intragastric administration in healthy foals.
Animals—6 healthy neonatal foals.
Procedures—Each foal received GaM (20 mg/kg) by intragastric administration. Blood samples were obtained before (time 0) and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, and 48 hours after GaM administration for determination of serum gallium concentrations by use of inductively coupled plasma mass spectroscopy.
Results—Mean ± SD pharmacokinetic variables were as follows: peak serum gallium concentration, 1,079 ± 311 ng/mL; time to peak serum concentration, 4.3 ± 2.0 hours; area under the serum concentration versus time curve, 40,215 ± 8,420 ng/mL/h; mean residence time, 39.5 ± 17.2 hours; area under the moment curve, 1,636,554 ± 931,458 ng([h]2/mL); and terminal half-life, 26.6 ± 11.6 hours. The mean serum concentration of gallium at 12 hours was 756 ± 195 ng/mL.
Conclusions and Clinical Relevance—Gallium maltolate administered via nasogastric tube at a dose of 20 mg/kg to neonatal foals resulted in gallium serum concentrations considered sufficient to suppress growth or kill Rhodococcus equi in macrophages and other infected tissues.
Abstract
Objective—To determine the pharmacokinetics of gallium maltolate (GaM) after intragastric administration in adult horses.
Animals—6 adult horses.
Procedures—Feed was withheld for 12 hours prior to intragastric administration of GaM (20 mg/kg). A single dose of GaM was administered to each horse via a nasogastric tube (time 0). Blood samples were collected at various time points from 0 to 120 hours. Serum was used to determine gallium concentrations by use of inductively coupled plasma-mass spectroscopy. Noncompartmental and compartmental analyses of serum gallium concentrations were performed. Pharmacokinetic models were selected on the basis of the Akaike information criterion and visual analysis of plots of residuals.
Results—Serum concentration data for 1 horse were such that this horse was considered an outlier and excluded from noncompartmental and compartmental analyses. Noncompartmental analysis was used to determine individual pharmacokinetic parameters. A 1-compartment model with first-order input and output and lag time was selected as the best-fit model for the data and used to determine mean — SD values for maximum observed serum concentration (0.28 — 0.09 μg/mL), time of maximum concentration (3.09 — 0.43 hours), time to the first measurable concentration (0.26 — 0.11 hours), apparent elimination half-life (48.82 — 5.63 hours), area under the time-concentration curve (20.68 — 757 h—μg/mL), and apparent volume of distribution (73,493 — 18,899 mL/kg).
Conclusion and Clinical Relevance—Further studies are necessary to determine the bioavailability of GaM after intragastric administration in adult horses.
Abstract
Objective—To determine the chemoprophylactic effect of gallium maltolate on the cumulative incidence of pneumonia caused by Rhodococcus equi infection in foals.
Animals—483 foals born and raised on 12 equine breeding farms with a history of endemic R equi infections.
Procedures—Group 1 foals were treated with a placebo and group 2 foals were treated with gallium maltolate (approx 30 mg/kg, PO, q 24 h) during the first 2 weeks after birth. Foals were monitored for development of pneumonia attributable to R equi infection and for adverse effects of gallium maltolate.
Results—There were no significant differences in the cumulative incidence of R equi pneumonia among the 2 groups.
Conclusions and Clinical Relevance—Chemoprophylaxis via gallium maltolate administered orally at approximately 30 mg/kg daily for the first 2 weeks after birth failed to reduce the cumulative incidence of pneumonia attributable to R equi infection among foals on breeding farms with endemic R equi infections. Further investigation is needed to identify strategies for control of R equi infections.
