Effect of omeprazole paste on gastric acid secretion in horses.

In a multicentre trial, 13 cannulated horses were treated orally once daily with a paste that delivered omeprazole at a dose of 4 and 5 mg/kg bwt in a 2-period crossover design to evaluate steady state gastric acid suppression. In each period, basal (unstimulated) and pentagastrin-stimulated gastric output were evaluated at 5-8 h after 5 doses, at 13-16 h after 10 doses, and at 21-24 h after 15 doses. Baseline data for gastric acid secretion were collected once for each horse in the month prior to initiation of omeprazole treatment. The inhibition of gastric acid secretion relative to baseline values, following treatment with omeprazole, were calculated and expressed as per cent. Pharmacokinetic data were also collected in this trial. At 4 mg/kg bwt, the oral paste formulation of omeprazole inhibited both basal and pentagastrin-stimulated gastric acid secretion by 99% at 5-8 h after treatment and by 83% (basal) and 90% (pentagastrin-stimulated) at 21-24 h. Inhibition following the administration of omeprazole at a dose of 5 mg/kg bwt was not significantly greater than when given at 4 mg/kg bwt. The results from this study could possibly lead to the development of an effective and practical antisecretory treatment of ulcer disease in horses.

Efficacy of omeprazole paste in the treatment and prevention of gastric ulcers in horses.

Equine gastric ulcer syndrome (EGUS) is very common among performance horses, with a reported prevalence of approximately 90% in racehorses, and also > 50% in foals. Omeprazole, an acid pump inhibitor 5 times more potent than ranitidine, has been used with great success to treat EGUS. This multicentre study of Thoroughbred racehorses with endoscopically verified gastric ulcers was designed to demonstrate the efficacy of an equine oral paste formulation of omeprazole in the treatment and prevention of recurrence of EGUS. Of the 100 horses entered into the study, 25 were sham-dosed for the full 58 days of the study. The remaining 75 horses all received omeprazole paste, 4 mg/kg bwt/day once daily for 28 days. At Day 28, 25 of treated horses continued on this dosing regimen while 25 received a half dose (2 mg/kg bwt once daily) and 25 horses were sham-dosed. By Day 28, gastric ulcers were completely healed in 77% of omeprazole-treated horses, while 92% were significantly (P < 0.01) improved. In contrast, 96% of the sham-dosed horses still had gastric ulcers at Day 28. The improvement was maintained in horses that continued on either a full dose or half dose of omeprazole paste until Day 58. However, in those horses that were removed from omeprazole treatment at Day 28, the incidence and severity of the gastric ulcers at the end of the study were similar to those horses that did not receive the omeprazole paste. This study demonstrates that omeprazole paste, 4 mg/kg bwt per os, once daily, is highly effective in healing gastric ulcers in Thoroughbred racehorses and that either a full dose or half dose of omeprazole paste effectively prevents the recurrence of EGUS. The study also indicates that gastric ulcers in untreated horses did not demonstrate a significant rate of spontaneous healing.

Effects of enalapril on exercise tolerance and longevity in dogs with heart failure produced by iatrogenic mitral regurgitation.

This study was conducted to evaluate the effects of enalapril on exercise capacity and longevity in dogs with left-sided heart failure produced by iatrogenic mitral regurgitation. After surgical creation of mitral regurgitation, 18 dogs were allocated into replicates according to exercise capacities. One dog in each replicate received placebo, and the other received 0.5 mg/kg of enalapril sid for 9 days and bid thereafter. Exercise tolerance was studied after 10, 19, 52 to 53, and 80 to 81 days, respectively. Finally, the percentage of dogs in each group that survived 357 days was compared. The duration of exercise for dogs in the placebo and enalapril groups did not differ at baseline (P > .1) or after 19 days (P > .1). Dogs that received enalapril had significantly reduced (P < .001) exercise tolerance at day 10, and significantly increased (P = .002) exercise tolerance at days 52 to 53 and 80 to 81 when compared with controls. At 357 days, 22% of dogs receiving placebo were alive, compared with 67% of dogs receiving enalapril; however, these differences were not statistically significant (P = .124). This study shows that enalapril increases exercise tolerance in dogs with left-sided heart failure induced by iatrogenic mitral regurgitation.

Efficacy of ivermectin in a beef-based chewable formulation against Ancylostoma caninum and Uncinaria stenocephala in dogs.

The effective dosage of a chewable formulation of ivermectin was determined in 35 young dogs with induced infections of Ancylostoma caninum and Uncinaria stenocephala. Dogs were inoculated with these parasites and held until the infections were patent. Within each of 7 replicates, dogs were allocated randomly to 1 of 5 treatment groups: vehicle control, or ivermectin at 6, 12, 18, or 24 micrograms/kg. Chewable treatments were tailored to body weight. Seven or 8 days after treatment, parasites were recovered using standard techniques. All 7 controls had adult A. caninum (geometric mean = 35.5) and U. stenocephala (geometric mean = 82.6). Against A. caninum, the efficacy of ivermectin was 52%, 98%, 95%, and 97% at 6, 12, 18, and 24 micrograms/kg, respectively. The statistical model that best described the dose response was linear to 12 micrograms/kg with a plateau thereafter. Using this model, the estimated reduction from the predicted control mean was 97.2%; the estimated dose to eliminate 90% of the worms (ED90) was 8.4 micrograms/kg, and the ED95 was 10.5 micrograms/kg. Against U. stenocephala, the dose response was linear in the range studied, with an ED90 of 20.8 micrograms/kg; it was estimated that 93.2% of the worms would be eliminated.

Efficacy of ivermectin and pyrantel pamoate combined in a chewable formulation against heartworm, hookworm, and ascarid infections in dogs.

Eight trials were conducted in dogs to document the efficacy of ivermectin (6 micrograms/kg of body weight) and pyrantel pamoate (5 mg of active pyrantel/kg) in a beef-based chewable formulation against Dirofilaria immitis, Ancylostoma caninum, Uncinaria stenocephala, Toxocara canis, and Toxascaris leonina. Three studies involved induced infection with D immitis, and 5 studies involved induced or natural infection with hookworms and ascarids. In 3 intestinal parasite trials, the efficacy of the combination chewable tablet was compared with each of its components. Results indicated that 1 component did not interfere with the activity of the other. In 1 heartworm and 2 intestinal parasite trials, the efficacy of pyrantel, ivermectin/pyrantel combination, or ivermectin with pyrantel dosage of 10 mg/kg was evaluated. The ivermectin/pyrantel combination was 100% effective in preventing development of D immitis larvae. Efficacy of the combined product against T canis, Toxascaris leonina, A caninum, and U stenocephala was 90.1, 99.2, 98.5, and 98.7%, respectively. In the intestinal parasite trials, each individual component was found not to interfere with the anthelmintic action of the other. Increasing the dosage of pyrantel to 10 mg/kg (2 x that in the combination) did not interfere with the efficacy of ivermectin against heartworm or increase the activity of pyrantel against intestinal parasites.

Safety study of a beef-based chewable tablet formulation of ivermectin and pyrantel pamoate in growing dogs, pups, and breeding adult dogs.

To determine the safety of a new combination of ivermectin and pyrantel (as pamoate salt) in a novel beef-based chewable tablet formulation, 3 tolerance trials were conducted and included growing dogs, pups, and breeding adult dogs. Growing dogs, given the combination orally for 5 consecutive days at recommended dosages (5 mg of pyrantel/kg of body weight, 6 micrograms of ivermectin/kg) or at twice the pyrantel dosage in combination with the recommended dosage of ivermectin, had no adverse effects. The combination also was administered to 6-week-old pups at 1, 3, and 5 times the recommended dose on 3 successive days for 3 times in 1 month. Compared with age-matched controls, treatment had no effect on clinical status, growth rate, or gross or histologic features. Breeding male and female dogs given the combination at 3 times the recommended dose for extended periods had no adverse effects, and prevalence of abnormalities in the offspring was not greater than that in nonmedicated controls.

Efficacy of an ivermectin/pyrantel pamoate chewable formulation against the canine hookworms, Uncinaria stenocephala and Ancylostoma caninum.

The effectiveness of the combination of pyrantel pamoate (5 mg kg-1) and ivermectin (6 micrograms kg-1) against the canine hookworms Uncinaria stenocephala and Ancylostoma caninum was determined. This combination is intended for monthly use as a heartworm preventative and for treatment and control of canine hookworms. The formulation was found to be effective (99.6% reduction in worm burdens) against both species of hookworms in experimentally infected dogs. No adverse effects due to the drug combination were observed in any dog during the course of this study.

Bioavailability of ivermectin administered orally to dogs.

The bioavailability of three formulations of ivermectin was determined following oral administration to dogs. The average peak plasma level (Cmax) of ivermectin administered in the standard tablet formulation at 6 and 100 micrograms/kg of body weight was 2.97 and 44.31 ng/g, respectively. This suggest dose-dependent pharmacokinetics. Cmax and total ivermectin bioavailability, as assessed from the area under the plasma curve (AUC), were similar between two tablet formulations of ivermectin administered at 100 micrograms/kg. Furthermore, Cmax was similar following administration of radiolabelled ivermectin at 6 micrograms/kg in either a beef-based chewable formulation or in the standard tablet formulation.

Evaluation of a beef-based chewable formulation of pyrantel pamoate against induced and natural infections of hookworms and ascarids in dogs.

Pyrantel pamoate, formulated in a beef-based chewable tablet, was evaluated for efficacy in dogs against induced and natural infections of Toxocara canis, Toxascaris leonina, Ancylostoma caninum and Uncinaria stenocephala. Dose titration trials were conducted in Canada, the UK and Germany in dogs treated with pyrantel (as pamoate salt) at 0, 2.5, 5 or 10 mg kg-1 body weight. These studies showed that a dose rate of 2.5 mg kg-1, the efficacy of pyrantel against adult T. canis, T. leonina, U. stenocephala and A. caninum was 76.1, 85.6, 100 and 87.9%, respectively. Efficacy at 5 mg kg-1 against the same parasites was 94.2, 92.0, 93.5 and 93.8%, respectively, and at 10 mg kg-1 efficacy was 91.2, 97.6, 98.7 and 91.3%, respectively. No adverse effects due to treatment were seen in any of these trials.

Reproductive evaluation of male beagles and the safety of ivermectin.

Ivermectin had no adverse effects on spermatogenesis, fertility, or reproductive performance of Beagle dogs when administered orally at 600 micrograms/kg (0.6 mg/kg) of body weight monthly for 8 treatments. Semen was collected every 3 days from 28 days before treatment began until 83 days thereafter from 6 ivermectin-treated Beagles and 6 similar water-treated controls (38 collections/dog). All dogs were then bred to 2 nontreated bitches each; litter size, birth weights, and pup abnormalities and mortalities were evaluated. After all pups were whelped, each dog was euthanatized and necropsied, and the testis and epididymis were examined microscopically.

A double-blind randomized placebo controlled gastroscopic study to compare the effects of indomethacin capsules and indomethacin suppositories on the gastric mucosa of human volunteers.

Forty-five normal volunteers were divided into 3 equal groups, each receiving indomethacin or placebo once daily in he evening as a capsule or suppository for 10 days. The dose of indomethacin was 50 mg for the first 5 days and 100 mg for the second 5 days. Endoscopic evaluation of the gastric mucosa was carried out on days 1, 6 and 11. It was found that indomethacin capsules caused significantly more gastric irritation than indomethacin suppositories (p less than .01) or placebo (p less than .0001). No significant difference was found in the incidence of gastric injury observed in the indomethacin suppository and placebo groups.