Gigi S. Davidson

Amantadine in a Multimodal Analgesic Regimen for Alleviation of Refractory Osteoarthritis Pain in Dogs

BACKGROUND Nonsteroidal anti-inflammatory drugs (NSAIDs) do not always provide sufficient pain relief in dogs with osteoarthritis (OA). HYPOTHESIS The use of amantadine in addition to NSAID therapy will provide improved pain relief when compared with the use of nonsteroidal analgesics alone in naturally occurring OA in dogs. ANIMALS Thirty-one client-owned dogs with pelvic limb lameness despite the administration of an NSAID. METHODS The study was randomized, blinded, and placebo controlled with parallel groups (days 21-42). On day 0, analgesic medications were discontinued. On day 7, all dogs received meloxicam for 5 weeks. On day 21, all dogs received amantadine (3-5 mg/kg once daily per os) or placebo for 21 days, in addition to receiving meloxicam. Assessments were performed before the study and on days 7, 21, and 42. Primary outcome measures were blinded owner assessments of activity using client-specific outcome measures (CSOM) on days 0, 7, 21, and 42. Data were analyzed by a mixed model approach. RESULTS For CSOM activity, there was a significant time by treatment effect (P=.009). On the basis of the planned post hoc t-tests of postrandomization means, there was a significant difference between treatment groups on day 42 (P=.030), with the amantadine group being more active. CONCLUSIONS AND CLINICAL IMPORTANCE In dogs with osteoarthritic pain refractory to an NSAID, physical activity is improved by the addition of amantadine. Amantadine might be a useful adjunct therapy for the clinical management of canine osteoarthritic pain.

Efficacy of Oral Famotidine and 2 Omeprazole Formulations for the Control of Intragastric pH in Dogs

BACKGROUND Little is known about the efficacy of commonly used acid suppressants on intragastric pH in dogs. OBJECTIVE To compare the effect of oral famotidine, 2 formulations of omeprazole, and placebo on intragastric pH in dogs with a catheter-free, continuous pH monitoring system. ANIMALS Six healthy adult mixed-breed colony dogs. METHODS Utilizing a randomized, 4-way cross over, open-label study, dogs were administered famotidine PO (1.0-1.3 mg/kg q12h), omeprazole tablet (1.5-2.6 mg/kg q24h), omeprazole reformulated paste (RP) (Gastrogard, 1.5-2.6 mg/kg q24h), and placebo for 7 days followed by a 10-day washout period. Radiotelemetric pH capsules were placed with gastroscopy assistance to continuously record intragastric pH for 4 days (days 4-7 of dosing). The percentage of time that intragastric pH was ≥3 and ≥4 was compared among treatment groups using repeated measures of analysis of variance. Tukeys Studentized range test was used to determine which groups were different with α= 0.05. RESULTS Mean ± SD percent time intragastric pH was ≥3 and ≥4 was 22 ± 8% and 14 ± 6% for famotidine, 63 ± 14% and 52 ± 17% for omeprazole tablet, 54 ± 17% and 44 ± 18% for omeprazole RP, and 6 ± 6% and 5 ± 5% for placebo. Both omeprazole formulations significantly increased intragastric pH compared with famotidine and placebo, but omeprazole tablet and RP was not significantly different from each other. CONCLUSION Oral omeprazole tablet and RP provide superior gastric acid suppression to famotidine, and should therefore be considered more effective for the treatment of acid related disorders in dogs.

Dose reduction of meloxicam in dogs with osteoarthritis-associated pain and impaired mobility.

BACKGROUND Progressive nonsteroidal anti-inflammatory drug (NSAID) dose reduction appears logical; however, there is no evidence-based medicine indicating that efficacy is maintained as dose is reduced. OBJECTIVE To determine if NSAID dose can be reduced and pain relief and mobility can be maintained in dogs with osteoarthritis (OA). ANIMALS Client-owned dogs (n = 59) with OA-associated impaired mobility and pain. METHODS Prospective, randomized, blinded study. After 14 days wash-out, dogs were randomized to reducing dose (RDG) (n = 30) or maintenance dose (MDG) (n = 29). MDG received standard dose meloxicam. RDG received a reducing dose from D28 onward, reducing to 0% of maintenance for the final 2 weeks. Assessments were at D14, 28, 42, 56, 70, 84, 98 and 112 using subjective owner assessments, accelerometry (AM), and standing percent body weight distribution (%BW). A Kaplan-Meier survival curve described how dogs dropped out because of insufficient pain control. A Log-rank test compared the groups. RESULTS More dogs in RDG (13) dropped out because of owner-evaluated insufficient pain control compared with MDG (5) (P = .029; odds ratio: 3.67; median dropout time: 84 days in each group). For the dogs that did not drop out (n = 41), there were no significant differences between groups in owner assessments (P > .2 for each), %BW placed on the index limb (P = .750), or accelerometer-measured activity (P = .14). CONCLUSION AND CLINICAL RELEVANCE Dose reduction is a less effective means of pain control compared with maintained dosing. However, NSAID dose reduction with maintained efficacy is possible, but success appears to be individual dog dependent.

Feline Musculoskeletal Pain Index: Responsiveness and Testing of Criterion Validity

BACKGROUND Progress in establishing if therapies provide relief to cats with degenerative joint disease (DJD)-associated pain is hampered by a lack of validated owner-administered assessment methods. HYPOTHESIS That an appropriately developed subjective owner-completed instrument (Feline Musculoskeletal Pain Index-FMPI) to assess DJD-associated impairment would have responsiveness and criterion validity. ANIMALS Twenty-five client-owned cats with DJD-associated pain. METHODS FMPI responsiveness (ability to detect the effect of an analgesic treatment) and validity (correlation with an objective measure) were explored through a stratified, randomized, double blinded, placebo-controlled, crossover 10-week clinical study. Meloxicam was administered to effect pain relief. A linear mixed model, backward stepwise regression, and Pearson correlations were used to assess responsiveness and criterion validity with the assumption that the NSAID would increase activity. RESULTS Positive responses of cats to placebo (P = .0001) and meloxicam treatment (P = .0004) were detected; however, the instrument did not detect any difference between placebo and meloxicam (linear mixed model), even for the high impairment cases. Percent meloxicam target dose administered, temperament, and total baseline FMPI score were covariates that most affected FMPI scores. Controlling for significant covariates, most positive effects were seen for placebo treatment. Positive treatment effects on activity were detected, but only for the cases designated as most highly impaired. CONCLUSIONS AND CLINICAL IMPORTANCE Neither responsiveness nor criterion validity were detected by the inclusion criteria for cases in this study. The data suggest that further work is indicated to understand factors affecting activity in cats to optimize inclusion criteria.

Evaluation of a Midhumeral Block of the Radial, Ulnar, Musculocutaneous and Median (RUMM Block) Nerves for Analgesia of the Distal Aspect of the Thoracic Limb in Dogs

OBJECTIVE To evaluate a technique for midhumeral peripheral nerve blockade in the dog. STUDY DESIGN Cadaveric technique development; in vivo placebo-controlled, prospective crossover study. ANIMALS Canine cadavers (n=38) and 8 clinically healthy, adult hound dogs. METHODS A technique for peripheral block of the radial, ulnar, musculocutaneous, and median nerves (RUMM block) was evaluated using cadaver limbs. Eight purpose-bred, research dogs were anesthetized; a RUMM block was performed on each thoracic limb. One limb from each dog randomly received 0.5% bupivacaine and the opposite limb was assigned to receive sterile saline solution as a control. After recovery from anesthesia, skin sensation at selected dermatomes was evaluated for 24 hours using a mechanical stimulus. Weight-bearing, conscious proprioception, and withdrawal reflex were also evaluated. One month after initial testing, each dog was reanesthetized and each limb received the opposite treatment. RESULTS Sensory thresholds were significantly increased over baseline measurements when compared with control limbs for all nerves. Complete sensory block was achieved in radial (15/16), ulnar (3/16), musculocutaneous (8/16), and median (11/16) nerves, using a mechanical stimulus of analgesia. Complete simultaneous block of all nerves was only obtained in 1 of 16 limbs. CONCLUSION RUMM block resulted in desensitization of the skin in the associated dermatomes for 4-10 hours. Complete sensory block of the dermatomes supplied by the radial nerve was most consistent. CLINICAL RELEVANCE RUMM block may be an effective technique to provide adjunctive analgesia for dogs undergoing surgery of the distal aspect of the thoracic limb.

Ronidazole pharmacokinetics after intravenous and oral immediate-release capsule administration in healthy cats⋆

Ronidazole (RDZ) is an effective treatment for feline Tritrichomonas foetus infection, but has produced neurotoxicity in some cats. An understanding of the disposition of RDZ in cats is needed in order to make precise dosing recommendations. Single-dose pharmacokinetics of intravenous (IV) RDZ and immediate-release RDZ capsules were evaluated. A single dose of IV RDZ (mean 9.2 mg/kg) and a 95 mg immediate-release RDZ capsule (mean 28.2 mg/kg) were administered to six healthy cats in a randomized crossover design. Plasma samples were collected for 48 h and assayed for RDZ using high pressure liquid chromatography (HPLC). Systemic absorption of oral RDZ was rapid and complete, with detection in the plasma of all cats by 10 min after dosing and a bioavailability of 99.64 (±16.54)%. The clearance of RDZ following IV administration was 0.82 (±0.07) ml/kg/min. The terminal half-life was 9.80 (±0.35) and 10.50 (±0.82) h after IV and oral administration, respectively, with drug detectable in all cats 48 h after both administrations. The high oral bioavailability of RDZ and slow elimination may predispose cats to neurotoxicity with twice-daily administration. Less frequent administration should be considered for further study of effective treatment of T foetus-infected cats.

Successful management of gastrointestinal pythiosis in a dog using itraconazole, terbinafine, and mefenoxam

Medical therapy for pythiosis is hampered by a lack of efficacious drugs. The present report describes a case of canine gastrointestinal pythiosis in which lesions were resolved through the administration of itraconazole, terbinafine, and the agricultural fungicide mefenoxam. No substantial adverse effects occurred in association with administration of the latter compound. Additional studies are needed to evaluate the pharmacokinetics of mefenoxam and to further assess its tolerability and potential efficacy for the treatment of pythiosis in dogs.

Effects of compounding and storage conditions on stability of pergolide mesylate

OBJECTIVE To determine the effects of temperature and light over a 35-day period on stability of pergolide mesylate after compounding in an aqueous vehicle. DESIGN Evaluation study. PROCEDURES Pergolide was compounded into a formulation with a final target concentration of 1 mg/mL. Aliquots of the formulation were then stored at -20 degrees, 8 degrees, 25 degrees, or 37 degrees C without exposure to light or at 25 degrees C with exposure to light for 35 days. Samples were assayed in triplicate by means of high-pressure liquid chromatography immediately after compounding and after 1, 7, 14, 21, and 35 days of storage. RESULTS Mean+/-SD concentration of pergolide in the formulation immediately after compounding was 1.05+/-0.086 mg/mL. Samples exposed to light while stored at 25 degrees C had undergone excessive degradation by day 14, samples stored at 37 degrees C had undergone excessive degradation by day 21, and samples stored at 25 degrees C without exposure to light had undergone excessive degradation by day 35. The decrease in expected concentration corresponded with the appearance of degradation peaks in chromatograms and with a change in color of the formulation. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that pergolide mesylate was unstable after compounding in an aqueous vehicle and that storage conditions had an effect on stability of the compounded formulation. Compounded pergolide formulations in aqueous vehicles should be stored in a dark container, protected from light, and refrigerated and should not be used >30 days after produced. Formulations that have undergone a color change should be considered unstable and discarded.

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).

Evaluation of the Effect of Orally Administered Acid Suppressants On Intragastric pH in Cats

Background Acid suppressant drugs are a mainstay of treatment for cats with gastrointestinal erosion and ulceration. However, clinical studies have not been performed to compare the efficacy of commonly PO administered acid suppressants in cats. Hypothesis/Objectives To compare the effect of PO administered famotidine, fractionated omeprazole tablet (fOT), and omeprazole reformulated paste (ORP) on intragastric pH in cats. We hypothesized that both omeprazole formulations would be superior to famotidine and placebo. Animals Six healthy adult DSH colony cats. Methods Utilizing a randomized, 4‐way crossover design, cats received 0.88–1.26 mg/kg PO q12h fOT, ORP, famotidine, and placebo (lactose capsules). Intragastric pH monitoring was used to continuously record intragastric pH for 96 hours beginning on day 4 of treatment. Plasma omeprazole concentrations at steady state (day 7) were determined by high performance liquid chromatography (HPLC) with ultraviolet detection. Mean percentage time that intragastric pH was ≥3 and ≥4 were compared among groups using ANOVA with a posthoc Tukey‐Kramer test (α = 0.05). Results The mean percentage time ± SD that intragastric pH was ≥3 was 68.4 ± 35.0% for fOT, 73.9 ± 23.2% for ORP, 42.8 ± 18.6% for famotidine, and 16.0 ± 14.2% for placebo. Mean ± SD plasma omeprazole concentrations were similar in cats receiving fOT compared to those receiving ORP and in a range associated with acid suppression reported in other studies. Conclusions and Clinical Importance These results suggest that both omeprazole formulations provide superior acid suppression in cats compared to famotidine or placebo. Fractionated enteric‐coated OT is an effective acid suppressant despite disruption of the enteric coating.