Assessment of clotrimazole gels for in vitro stability and in vivo retention in the frontal sinus of dogs.

OBJECTIVE: To evaluate the stability and retention of viscous formulations of the antifungal drug clotrimazole in vitro and to evaluate retention times, absorption, and histologic response to these compounds when placed in the frontal sinus of dogs. ANIMALS: 6 male Beagles. PROCEDURES: 1% clotrimazole gels were formulated with hydroxypropyl cellulose, poloxamer, and carboxymethylcellulose sodium bases. Commercially available 1% clotrimazole creams were also evaluated. Each compound was incubated at 37 degrees C in a funnel. Volume retained and clotrimazole stability were evaluated for 4 weeks. Six compounds were then chosen for in vivo evaluation. The frontal sinuses of 6 dogs were filled with 1 of the 6 compounds. Computed tomographic evaluation was performed weekly for up to 4 weeks to evaluate gel retention. Blood samples were collected to evaluate clotrimazole absorption. Following euthanasia, sinuses were examined histologically. RESULTS: Commercially available clotrimazole creams were not retained in funnels in vitro. In vivo, hydroxypropyl cellulose- and carboxymethylcellulose-based gels resulted in the most severe inflammatory response and were retained the longest. Poloxamer-based gels had a shorter retention time and were associated with less inflammation. Clotrimazole was minimally absorbed. Despite a marked inflammatory response to several of the clotrimazole-containing gels, no notable adverse clinical responses were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Poloxamer gels had the most promise for improving drug contact within the frontal sinus of dogs, while limiting the inflammatory response. Poloxamer gels have the additional benefit of improved handling as a result of reverse gelation (ie, they gel when warmed to 37 degrees C).

Pharmacokinetics and pharmacodynamics of furosemide after oral administration to horses.

Furosemide is the most common diuretic drug used in horses. Furosemide is routinely administered as IV or IM bolus doses 3-4 times a day. Administration PO is often suggested as an alternative, even though documentation of absorption and efficacy in horses is lacking. This study was carried out in a randomized, crossover design and compared 8-hour urine volume among control horses that received placebo, horses that received furosemide at 1 mg/kg PO, and horses that received furosemide at 1 mg/kg IV. Blood samples for analysis of plasma furosemide concentrations, PCV, and total solids were obtained at specific time points from treated horses. Furosemide concentrations were determined by reversed-phase high-performance liquid chromatography with fluorescent detection. Systemic availability of furosemide PO was poor, erratic, and variable among horses. Median systemic bioavailability was 5.4% (25th percentile, 75th percentile: 3.5, 9.6). Horses that received furosemide IV produced 7.4 L (7.1, 7.7) of urine over the 8-hour period. The maximum plasma concentration of 0.03 microg/mL after administration PO was not sufficient to increase urine volume compared with control horses (1.2 L [1.0, 1.4] PO versus 1.2 L [1.0, 1.4] control). There was a mild decrease in urine specific gravity within 1-2 hours after administration of furosemide PO, and urine specific gravity was significantly lower in horses treated with furosemide PO compared with control horses at the 2-hour time point. Systemic availability of furosemide PO was poor and variable. Furosemide at 1 mg/kg PO did not induce diuresis in horses.