In vitro cytotoxicity and antiviral efficacy against feline herpesvirus type 1 of famciclovir and its metabolites.

OBJECTIVES: To assess in vitro the antiviral efficacy against feline herpesvirus (FHV-1) and cytotoxicity for cultured feline cells of famciclovir and its metabolites, BRL 42359 and penciclovir. To investigate the effect of timing of penciclovir application on in vitro antiviral activity. PROCEDURES: Plaque reduction assays were used to estimate antiviral efficacy of all compounds and the effect of penciclovir exposure before or after exposure to a FHV-1 field isolate. Cytotoxicity was evaluated by assessing cell morphology and viable cell number for 72 h following exposure to each compound. RESULTS: The penciclovir concentration that inhibited FHV-1-induced plaque formation by 50% (IC50 ) was 0.86 µg/mL (3.4 µm). Famciclovir and BRL 42359 had no antiviral effect against FHV-1 at any concentration assessed. Antiviral activity was significantly enhanced when cells were exposed to 4 µm penciclovir (approximate IC50 ) for 1 h but not for 24 h before viral adsorption. Delaying exposure of cells to penciclovir for 1, 2, or 4 h after viral adsorption significantly enhanced antiviral activity. Relative to untreated control wells, >88% of cells remained viable when exposed to famciclovir (100 µm), BRL 42359 (1.06 mm), or penciclovir (40 µm) for 72 h. No morphologic evidence of cytotoxicity was noted. CONCLUSIONS: Penciclovir demonstrates potent antiviral activity against FHV-1 and may be effective at lower tissue, tear, and plasma concentrations than previously targeted. The duration of in vitro antiviral effect of penciclovir suggests that frequent famciclovir administration may be necessary in vivo. Famciclovir and BRL 42359 showed no signs of in vitro cytotoxicity.

Effects of postanesthetic sedation with romifidine or xylazine on quality of recovery from isoflurane anesthesia in horses.

OBJECTIVE: To test the hypothesis that postanesthetic sedation with romifidine would dose-dependently improve recovery quality of recovery from isoflurane anesthesia in horses more than postanesthetic sedation with xylazine. DESIGN: Prospective, randomized, blinded clinical trial. ANIMALS: 101 healthy adult horses examined at the University of California-Davis Veterinary Medical Teaching Hospital from 2007 to 2009. PROCEDURES: Horses were sedated with xylazine, and anesthesia was induced with guaifenesin, diazepam, and ketamine via a standardized drug protocol. Anesthesia for surgical or diagnostic procedures was maintained with isoflurane in oxygen for 1 to 4 hours. At the end of anesthesia, horses were moved to a padded stall for recovery. Once the breathing circuit was disconnected and the patient was spontaneously breathing, either xylazine (100 or 200 µg/kg [45 or 91 µg/lb]) or romifidine (10 or 20 µg/kg [4.5 or 9.1 µg/lb]) was administered i.v.. Objective patient, surgical, and anesthesia data were recorded. Subjective visual analog scale (VAS) scores of recovery quality were assigned by a single individual who was unaware of the treatment received. A stepwise linear regression model was used to correlate patient and procedure factors with the VAS score. RESULTS: Painful procedures, longer anesthesia times, and the Arabian horse breed were associated with poorer VAS scores. Adjustment for these factors revealed an improved VAS recovery score associated with the use of a romifidine dose of 20 µg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy adult horses anesthetized with isoflurane for > 1 hour, the results of this study supported the use of 20 µg of romifidine/kg, i.v., rather than lower romifidine doses or xylazine, for postanesthetic sedation to improve recovery quality.

Stability and uniformity of extemporaneous preparations of voriconazole in two liquid suspension vehicles at two storage temperatures.

OBJECTIVE: To determine the stability and distribution of voriconazole in 2 extemporaneously prepared (compounded) suspensions stored for 30 days at 2 temperatures. SAMPLE POPULATION: Voriconazole suspensions (40 mg/mL) compounded from commercially available 200-mg tablets suspended in 1 of 2 vehicles. One vehicle contained a commercially available suspending agent and a sweetening syrup in a 1:1 mixture (SASS). The other vehicle contained the suspending agent with deionized water in a 3:1 mixture (SADI). PROCEDURES: Voriconazole suspensions (40 mg/mL in 40-mL volumes) were compounded on day 0 and stored at room temperature (approx 21 degrees C) or refrigerated (approx 5 degrees C). To evaluate distribution, room-temperature aliquots of voriconazole were measured immediately after preparation. Refrigerated aliquots were measured after 3 hours of refrigeration. To evaluate stability, aliquots from each suspension were measured at approximately 7-day intervals for up to 30 days. Voriconazole concentration, color, odor, opacity, and pH were measured, and aerobic and anaerobic bacterial cultures were performed at various points. RESULTS: Drug distribution was uniform (coefficient of variation, < 5%) in both suspensions. On day 0, 87.8% to 93.0% of voriconazole was recovered; percentage recovery increased to between 95.1% and 100.8% by day 7. On subsequent days, up to day 30, percentage recovery was stable (> 90%) for all suspensions. The pH of each suspension did not differ significantly throughout the 30-day period. Storage temperature did not affect drug concentrations at any time, nor was bacterial growth obtained. CONCLUSIONS AND CLINICAL RELEVANCE: Extemporaneously prepared voriconazole in SASS and SADI resulted in suspensions that remained stable for at least 30 days. Refrigerated versus room-temperature storage of the suspensions had no effect on drug stability.