Objective—To determine effects of SC administration
of repeated doses of a low molecular weight
heparin (LMWH) in dogs.
Animals—5 healthy dogs.
Procedure—Each dog received 6 injections (each
injection, 150 U of anti-factor-Xa [anti-FXa]/kg of body
weight, SC) at 8-hour intervals. Blood samples were
collected before and 2 hours after the first, second,
third, and sixth injections to measure heparin activity,
thrombin time, activated partial thromboplastin time
(APTT), antithrombin activity, Hct, and platelet count.
Results—Heparin activity varied between 0.36 ± 0.10
and 0.77 ± 0.08 U of anti-FXa/ml (before and 2 hours
after the third injection) and between 0.46 ± 0.11 and
0.82 ± 0.15 U of anti-FXa/ml (before and 2 hours after
the sixth injection). Thrombin time and APTT were
influenced only slightly. Platelet count, Hct, and
antithrombin activity started to decrease significantly
2 hours after the second LMWH injection. Because of
the increased consumption of antithrombin,
antithrombin activity continuously decreased from
102.1 ± 6.3% before the study to 91.0 ± 3.0% at the
end of the study.
Conclusion and Clinical Relevance—Heparin plasma
activity was only slightly higher than that recommended
for LMWH treatment of humans, and none
of the dogs had signs of increased bleeding. Thus,
administration of heparin in accordance with this dosing
regimen can be recommended for use in clinical
studies. The screening tests investigated were not
suitable for use in monitoring LMWH treatment of
dogs. Assays that use chromogenic substrates are
necessary to reliably monitor LMWH plasma concentrations
in dogs. (Am J Vet Res 2001;62:595–598)
OBJECTIVE To monitor concentrations of sulfadimidine in the paranasal sinus mucosa (PSM) of unsedated horses following IV administration of trimethoprim-sulfadimidine via in vivo microdialysis.
ANIMALS 10 healthy adult horses.
PROCEDURES Concentric microdialysis probes were implanted into the subepithelial layers of the frontal sinus mucosa of standing sedated horses. Four hours after implantation, trimethoprim-sulfadimidine (30 mg/kg) was administered IV every 24 hours for 2 days; dialysate and plasma samples were collected at intervals during that 48-hour period and analyzed for concentrations of sulfadimidine. The dialysate concentration and relative loss of sulfadimidine from the perfusate were used to calculate the PSM concentration.
RESULTS Microdialysis probe implantation and subsequent in vivo microdialysis were successfully performed for all 10 horses. Following the first and second administration of trimethoprim-sulfadimidine, mean ± SD peak concentrations of sulfadimidine were 55.3 ± 10.3 μg/mL and 51.5 ± 8.7 μg/mL, respectively, in plasma and 9.6 ± 4.5 μg/mL and 7.0 ± 3.3 μg/mL, respectively, in the PSM. Peak sulfadimidine concentrations in the PSM were detected at 5.9 ± 2.7 hours and 5.4 ± 2.3 hours following the first and second drug administrations, respectively. For 12 hours, mean PSM sulfadimidine concentration remained greater than the minimum inhibitory concentration indicative of sulfonamide susceptibility of equine bacterial isolates (4.75 μg/mL).
CONCLUSIONS AND CLINICAL RELEVANCE In vivo microdialysis for continuous monitoring of PSM sulfadimidine concentrations in unsedated horses was feasible. Intravenous administration of trimethoprim (5 mg/kg) and sulfadimidine (25 mg/kg) proved likely to be efficient for treating sinusitis caused by highly susceptible pathogens, providing that the dosing interval is 12 hours.