Comparative efficacy of triclabendazole, nitroxynil and rafoxanide against immature and mature Fasciola hepatica in naturally infected cattle

In two trials the fasciolicidal activities of triclabendazole, nitroxynil and rafoxanide were assessed in cattle naturally infected with predominantly immature stages of Fasciola hepatica. Tablets containing 900 mg triclabendazole were administered orally at a dose rate of 12 mg/kg bodyweight. Rafoxanide and nitroxynil were used at a dose rate of 10 mg/kg, rafoxanide being given orally and nitroxynil by subcutaneous injection. Based on faecal egg counts nine weeks after treatment the efficacies were calculated to be 100 per cent for triclabendazole and 95.0 per cent for nitroxynil in the first trial and 98.4 per cent for triclabendazole and 52.9 per cent for rafoxanide 15 weeks after treatment in the second trial. In the first trial five animals from each of the three groups were slaughtered and their fluke burdens counted. Compared with the untreated control group the reductions in the fluke burdens were 96.9 per cent in triclabendazole treated cattle and 76.4 per cent in the nitroxynil treated group.     

Pharmacokinetics of erythromycin in foals and in adult horses

The pharmacokinetic parameters of erythromycin in foals were determined following intravenous administration of 5.0 mg/kg to animals aged 1, 3, 5 and 7 weeks. The distribution of the drug was described by a two-compartment open model, and no significant differences were observed between coefficients on which the parameters were based. Pharmacokinetic values were also determined for four mares given 5.0 mg/kg intravenously and for six 10–12 week-old foals given 20.0 mg/kg intravenously. The half-life of erythromycin for all groups of animals (foals less than 7 weeks, mares, foals 10–12 weeks) was 1.0–1.1 h; the apparent volume of distribution was between 2.3 and 7.2 l/kg, and the clearance of the drug from the body was between 1.9 and 5.0 mg/kg/h. No drug could be detected in the serum following oral administration of 5.0 mg/kg erythromycin estolate; detectable levels were found for 5 h in mares given 12.5 mg/kg, and for 8 h in foals given 20.0 mg/kg orally. Peak levels in foals given the drug orally were 0.42 μg/ml at 120 min after administration. Foals given 10.0 mg/kg of erythromycin base intramuscularly had serum concentrations detectable 12 h later, the peak level achieved was 1.44 μg/ml serum 90 min after administration and concentrations exceeded 0.25 μg/ml for 6 h. In the mares the milk concentrations were approximately twice those in serum. Recommendations were made for drug dosage to be used in the treatment of Corynebacterium equi pneumonia of foals.     

Chemoprophylaxis of fascioliasis with triclabendazole

In a field experiment, moderate to heavy natural concomitant infections with immature and mature Fasciola hepatica were treated with triclabendazole at a dose rate of 10 mg/kg and an efficiency of 99.8% was achieved. Subsequent treatments of all susceptible farm animals at the same dose rate at intervals of eight to eleven weeks were carried out for 14 months; no patent infections could be detected in sheep and cattle during the whole period. Evidence is presented that pasture contamination with liver fluke was reduced to a negligible level for a further 12 months after the final treatment. It is suggested that, if regular treatments with triclabendazole are given within the pre-patent period of Fasciola hepatica infection for the whole season, the infection can be eradicated or reduced to such a low level that control of the disease could be maintained with less frequent strategic drenching for a considerable period.     

Disposition of oral clarithromycin in foals

Clarithromycin offers numerous advantages over erythromycin and thus, is an attractive alternative for the treatment of Rhodococcus equi infections in foals. The disposition of clarithromycin was investigated in 6 foals after intragastric administration at a dose of 10 mg/kg body weight. Detectable serum concentrations of clarithromycin were found in 3 of 6 foals at 10 minutes and in all foals by 20 minutes post-administration. Time to peak serum concentration (Tmax) was 1.5 hours and peak serum concentration (Cmax) was 0.92+/-0.17 microg/ml. Mean serum concentrations decreased to 0.03 microg/ml at 24 h. No adverse reactions were noted during or after IG administration in any of the foals. Based on the pharmacokinetic parameters, the MIC90 of R. equi isolates, and predicted steady state concentrations, an oral dose of 7.5 mg/kg given every 12 hours would appear appropriate for the treatment of R. equi infections in foals.     

Gentamicin dosage in foals aged one month and three months

The absorption and disposition kinetics of gentamicin were compared at two dosage levels (2 and 4 mg/kg bodyweight [bwt]) in one- and three-month-old foals. Following intramuscular (im) injection of single 2 mg/kg bwt doses, the drug was absorbed rapidly and produced peak serum concentration (18.2 mu 5.3 +/- g/ml, n = 8) at 30 mins. Much wider variations were associated with the amount of drug absorbed and the serum gentamicin concentrations after administration at the higher dosage level. The half-life of gentamicin was similar in the one-month-old (3.7 +/- 1.7 h, n = 8) and three-month-old (3.3 +/- 0.8 h, n = 8) foals, and was independent of the dose. One-month-old foals did not appear to have a deficiency in renal excretion of gentamicin. The minimum inhibitory concentration of gentamicin for Corynebacterium equi and certain other equine bacterial isolates was less than 0.195 microgram/ml. It was concluded that 2 mg/kg bwt administered by im injection at 8 to 12 h intervals, depending on the severity of the infection, could be recommended as the dose rate for treatment of systemic infections caused by microorganisms that are susceptible to gentamicin.     

Kinetic disposition of triclabendazole in buffalo compared to cattle

Concentrations of triclabendazole sulfoxide and its sulfone metabolite in plasma were measured in buffalo and cross-bred cattle after single intraruminal administration of triclabendazole at two different doses. Plasma concentrations of both metabolites were significantly lower in buffalo than cattle at both doses, which resulted in a smaller area under the concentration-time curve, a lower concentration maximum and a lower relative bioavailability. Thus, the recommended doses of 12 mg/kg body weight for the treatment of bubaline fascloliasis may not be valid for buffalo because of the substantially lower uptake of the drug in this species.     

Activity of closantel in the prevention of Gasterophilus and Strongylus vulgaris larval infections in equine foals and yearlings

Two controlled tests were conducted in equine foals and yearlings to determine the optimal oral dosage and the duration of activity of closantel for the prevention of Gasterophilus spp larval infections. Additional data were collected on the activity of closantel against Strongylus vulgaris larval infections. In experiment 1, 12 foals and 12 yearlings were equally allocated to 4 experimental groups, and were given oral treatments with closantel at dosages of 0 (nontreated controls), 2, 5, or 8 mg/kg of body weight every 2 months during bot season. The foals and yearlings were allowed to graze on open pasture throughout the experiment to provide a natural source for bot and helminth infections. All animals were euthanatized and necropsied 6 weeks after the final treatment. Closantel was highly effective (98.6% to 100%) at all doses in preventing Gasterophilus spp larval infections in the foals, but only the 8 mg/kg dose had significant (P less than 0.05) activity (99.7%) in the yearlings. This dose also significantly reduced the numbers of 4th-stage and immature adult S vulgaris (86.0%) in the mesenteric arteries as compared with nontreated controls. In experiment 2, 9 foals and 9 yearlings received a single oral treatment of 8 mg of closantel/kg of body weight; 3 foals and 3 yearlings were kept as nontreated controls. Groups of 6 treated (3 foals, 3 yearlings) and 2 control (1 foal, 1 yearling) animals were euthanatized and necropsied 1, 2, and 3 months after treatment. Closantel remained effective for 2 months in preventing infections of G intestinalis larvae in these foals and yearlings. Clinical signs of toxicosis were not observed in the treated animals of either study.     

Comparison of the efficacy of ivermectin, oxibendazole, and pyrantel pamoate against 28-day Parascaris equorum larvae in the intestine of pony foals

Sixteen helminth-free pony foals were inoculated with a mean (+/- SD) 2,000 (+/- 545.5) infective Parascaris equorum eggs (day 0). Foals were allocated to replicates of 4, and treatments within each replicate were assigned at random. Treatment administered on postinoculation day (PID) 28 included no treatment (control), 0.2 mg of ivermectin/kg of body weight, 10 mg of oxibendazole/kg, or 6.6 mg of pyrantel base (pamoate)/kg. Paste formulations of the anthelmintics were administered orally. The foals were euthanatized 14 days after treatment (PID 42) and examined for P equorum larvae in the small intestine. The mean +/- SD (and range) numbers of fourth-stage P equorum larvae recovered from nontreated foals and those treated with ivermectin, pyrantel, or oxibendazole were 1,603.8 +/- 1,026.8 (305 to 2,480), 29.3 +/- 55.8 (0 to 113), 413.0 +/- 568.1 (0 to 1,204), or 889.5 +/- 1,123.1 (1 to 2,345), respectively. Compared with the value for control (nontreated) foals, treatment with ivermectin, pyrantel, and oxibendazole was 98.2, 74.2, and 44.5% effective, respectively, when administered 28 days after experimentally induced infection with P equorum. Adverse reactions attributable to treatment were not observed.     

Critical tests and clinical trials on oxibendazole in horses with special reference to removal of Parascaris equorum.

The efficacy of oxibendazole given at dose level of 10 mg/kg of body weight was determined by 10 critical tests in foals and by 2 clinical trials in 20 foals (16 treated, 4 nontreated), with special interest in the drug activity against Parascaris equorum. The drug was uniformly efficacious (100%) against P equorum in the 10 critical-test foals, each having between 22 and 236 ascarids. Posttreatment reductions of ascarid egg counts in fecal samples were also 100% in suckling foals treated with oxibendazole given as a drench. Ascarid eggs did not reappear in fecal samples until the 8th week after foals were treated. A paste formulation of oxibendazole at 10 mg/kg also eliminated ascarid eggs from feces of 12 suckling foals. Strongyle EPG were markedly reduced by oxibendazole in the 10 critical-test foals and in 16 treated sucklings in the clinical trials. Egg and larval count data on foals in both the critical tests and the clinical trials also indicated oxibendazole was active against Strongyloides westeri. Untoward effects of treatment with oxibendazole were not observed.     

Comparative efficacy of closantel and triclabendazole against Fasciola hepatica in experimentally infected sheep

The effect of closantel (10 mg/kg orally) and triclabendazole (10 mg/kg orally) on the reappearance of a patent infection of Fasciola hepatica was studied in experimentally infected sheep. The treatments resulted in the interruption of faecal egg output for 11 weeks with triclabendazole and 13 weeks with closantel. Necropsy of untreated control animals revealed a mean burden of 360 flukes with a mean (+/- se) surface area of 171 +/- 64.3 mm2, whereas the fluke burdens in the closantel and triclabendazole-treated animals 14 weeks after treatment were 61 (83 per cent reduction) and 21 (94 per cent reduction), respectively. The surface areas of the flukes in the triclabendazole-group were comparable with the untreated controls (141 +/- 51.8 mm2), but the flukes in the closantel group were markedly smaller (43.1 +/- 26.9 mm2). It is concluded that closantel has, in epidemiological terms, a potency comparable with that of triclabendazole, despite its slightly lower efficacy against the very immature stages.     

Effects of repeated Strongylus vulgaris inoculations and concurrent ivermectin treatments on mesenteric arterial lesions in pony foals

Eight of 10 pony foals reared under helminth-free conditions were inoculated PO with 50 Strongylus vulgaris infective larvae/week for 4 weeks, at which time 1 foal died of acute verminous arteritis. Inoculation of 7 remaining foals continued at 2-week intervals for 20 weeks. Of the 7 foals, 3 were treated with ivermectin (0.2 mg/kg of body weight) in an oral paste formulation at experiment weeks 8, 16, 24; 4 foals were not treated. Two foals were not inoculated or treated and served as controls. After the first ivermectin treatment, ivermectin-treated foals had fewer days (12 +/- 2.9) with rectal temperatures greater than 38.6 C than did nontreated foals (23.3 +/- 3.8). Mean baseline rectal temperatures were 38 +/- 0.2 C. Adverse clinical reactions to ivermectin treatment were not observed in foals. Foals were euthanatized and necropsied 3 weeks after the last ivermectin treatment (week 24). Ivermectin was effective in reducing S vulgaris arterial larval and intestinal adult parasite numbers by 100% in 3 treated foals. Strongylus vulgaris arterial larvae and/or adults were recovered from all 4 nontreated inoculated foals. One nontreated inoculated foal lacked arterial larvae or active arterial lesions, indicating that protective resistance had developed in this individual. Marked gross and histopathologic lesions typical of chronic S vulgaris infection were observed in the 3 nontreated inoculated foals with arterial larvae. Repeated killing of intra-arterial S vulgaris fourth-stage larvae in ivermectin-treated foals did not exacerbate lesions associated with verminous arteritis or induce unique lesions associated with repeated destruction of arterial larvae.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of trimethoprim-sulphamethoxazole in two-day-old foals after a single intravenous injection

Six healthy two-day-old foals (3 pony foals and 3 horse foals) were given a single intravenous (iv) injection of trimethoprim (TMP)--sulphamethoxazole (SMZ) at a dosage of 2.5 mg of TMP/kg bodyweight (bwt) and 12.5 mg of SMZ/kg bwt. Serum TMP and SMZ concentrations were measured serially during a 24 hour period. The overall elimination rate constant (K) for TMP in the pony and horse foals was 0.45/h, whereas the K values for SMZ for the pony and horse foals were 0.12/h and 0.07/h, respectively (no significant difference; P greater than 0.05). Based on published minimum inhibitory concentration values for equine pathogens (Adamson et al 1985), the primary indication for the use of TMP/SMZ in foals may be in the treatment of infections caused by gram-positive bacteria. A dosage of 2.5 mg of TMP/kg bwt and 12.5 mg of SMZ/kg bwt, given iv at 12 h intervals would be appropriate.     

Evaluation of tulathromycin in the treatment of pulmonary abscesses in foals

Tulathromycin is a new injectable macrolide antibiotic used for the treatment of pulmonary diseases of swine and cattle. In this study, 37 foals with sonographic evidence of lung abscesses were treated with tulathromycin (2.5mg/kg intramuscularly [IM] once weekly, group 1) and 33 foals (group 2) with a combination of azithromycin (10mg/kg per os [PO] once daily for the first seven days of therapy, thereafter every other day) and rifampin (10mg/kg PO twice daily). The bacterial aetiological agent was not determined. The foals were only mildly sick and the median number of pulmonary abscesses was 1.4 (group 1) and 1.6 (group 2). Thirty foals in each group were treated without modifying therapy protocols until all clinical signs of disease had subsided. Tulathromycin was administered for a mean of 53 days, and azithromycin/rifampin for 42 days. The following side effects were associated with tulathromycin (279 IM injections): self-limiting diarrhoea in 11 foals; elevated temperature in six foals, and swellings at the injection site in 12 foals. This study provides some evidence that tulathromycin is well tolerated and appears promising for the treatment of pulmonary abscesses in foals.     

The efficacy of triclabendazole and other anthelmintics against Fasciola hepatica in controlled studies in cattle

In eight controlled tests 274 cattle were used to assess the efficacies of triclabendazole, albendazole, clorsulon, nitroxynil, oxyclozanide and rafoxanide against Fasciola hepatica. Against one-, two- and four-week-old early immature fluke the mean efficacies of triclabendazole given orally at 12 mg/kg were 88.1, 95.3 and 90.7 per cent, respectively. Clorsulon, nitroxynil and rafoxanide administered at recommended dose rates showed negligible activity against these stages of the parasite. Against six- and eight-week-old infections the mean efficacies of triclabendazole at 12 mg/kg were 87.5 per cent and 95.7 per cent, respectively. Against F hepatica aged six weeks, albendazole and oxyclozanide showed no activity and clorsulon, nitroxynil and rafoxanide had only slight to moderate activity. The efficacies of triclabendazole, clorsulon, nitroxynil and rafoxanide against 10- or 12-week-old parasites were 100, 99.0, 99.1 and 90.1 per cent, respectively. Albendazole and oxyclozanide showed poor efficacy against 12-week-old infections.     

An experimental study on triclabendazole resistance of Fasciola hepatica in sheep

The efficacy of triclabendazole in sheep experimentally infected with Fasciola hepatica was studied. Two groups of 12 lambs were infected with a susceptible (S) or a resistant (R) strain of F. hepatica. Eight weeks after infection, six lambs of each group (ST and RT) were treated with triclabendazole (10mg/kg). The other lambs were used as untreated controls (SC and RC). The parameters studied were: GLDH, gamma-GT, ELISA measuring antibodies against recombinant cathepsin-L(1) and eggs per gram faeces (epg). The lambs were slaughtered 16 weeks after infection and the number of flukes counted.The GLDH, gamma-GT levels and the OD value of the ELISA decreased as a result of the treatment in group ST. Patent infections were observed in all animals of groups SC, RT and RC. In group ST, occasionally a few eggs were found in five lambs. The percentage of flukes was 31.3 in SC and 37.6 in RC. In the treated groups ST and RT, the percentage of flukes was 0.06 and 33.6, respectively. These results corresponded to efficacies of 99.8% in the susceptible and 10.8% in the resistant strain. Since the resistant strain was isolated from a mixed cattle and sheep farm, it confirms the presence of triclabendazole resistance in the Netherlands.     

The activity of triclabendazole against immature and adult Fasciola hepatica infections in sheep

SUMMARY The efficiency of a new benzimidazole anthelmintic, triclabendazole, was tested against cumulative infections with Fasciola hepatica aged 1 to 12 weeks in sheep and compared with that of rafoxanide. At 10 mg/kg, triclabendazole was 99% effective in eliminating both immature and adult flukes. At a lower dose rate of 5 mg/kg, triclabendazole was highly effective against adults and significantly reduced the number of early immature flukes with an 87% overall reduction of fluke burden. Rafoxanide at 7.5 mg/kg showed high efficiency against adult fluke, but its effect on immatures was not significant, and overall efficiency was 64%.     

Chemoprophylaxis of fascioliasis with triclabendazole

In a field experiment, moderate to heavy natural concomitant infections with immature and mature Fasciola hepatica were treated with triclahendazole at a dose rate of 10 mg/kg and an efficiency of 99.8% was achieved. Subsequent treatments of all susceptible farm animals at the same dose rate at intervals of eight to eleven weeks were carried out for 14 months; no patent infections could be detected in sheep and cattle during the whole period. Evidence is presented that pasture contamination with liver fluke was reduced to a negligible level for a further 12 months after the final treatment. It is suggested that, if regular treatments with triclabendazole are given within the pre-patent period of Fasciola hepatica infection for the whole season, the infection can be eradicated or reduced to such a low level that control of the disease could be maintained with less frequent strategic drenching for a considerable period.     

Efficacy against Fasciola hepatica and the pharmacokinetics of triclabendazole administered by oral and topical routes

Objective   To determine the efficacy of triclabendazole (TCBZ) against 28-day-old, early immature liver fluke in cattle and its pharmacokinetics following administration by the oral or topical (pour-on) route.
Procedures   Cattle (n = 18) were infected with 500 TCBZ-susceptible liver fluke metacercariae and randomly allocated to three groups. At 28 days after infection, the groups were: (1) untreated controls; (2) treated with oral TCBZ at 12 mg/kg in combination with oxfendazole and selenium (TOS); (3) treated with pour-on TCBZ at 30 mg/kg in combination with abamectin (TA). Blood samples were taken immediately prior to treatment and serially after treatment to assess the plasma profile of TCBZ metabolites. Ten weeks after treatment all animals were slaughtered and total liver fluke counts, fluke egg counts and liver pathology were assessed.
Results   Both the TOS and TA treatments resulted in significant reductions of 28-day-old liver fluke, as assessed by fluke counts and fluke egg counts at slaughter, and the reductions following TOS treatment were significantly greater than those following TA treatment. The blood profile of TCBZ metabolites in TOS-treated animals showed a significantly greater area under the plasma concentration time curve and a higher maximum observed concentration than those treated with TA. There was significantly less liver pathology in TOS-treated animals than in the TA-treated animals.
Conclusion   TCBZ administered orally at 12 mg/kg resulted in greater efficacy against 28-day-old, early immature liver fluke than was achieved by topical administration at 30 mg/kg. Plasma metabolites of TCBZ were higher and liver pathology was less in TOS-treated animals than in TA-treated animals.     

The effect of omeprazole paste on intragastric pH in clinically ill neonatal foals

REASON FOR PERFORMING STUDY: Administration of omeprazole paste per os to healthy neonatal foals has been shown to effectively increase intragastric pH, but has not been evaluated in sick neonatal foals. OBJECTIVES: To determine the effect of orally administered omeprazole paste on intragastric pH in clinically ill neonatal foals requiring nasogastric intubation. METHODS: Intragastric pH was measured continuously for 24 h using an indwelling electrode and continuous data recording system in hospitalised neonatal foals age < or =2 days. Intragastric pH was measured for 12 h prior to (pretreatment period) and 12 h following (post treatment period) treatment with omeprazole paste (4 mg/kg bwt per os). All foals displayed periods of acidity (pH <4) prior to treatment. Statistical analysis compared pre- and post treatment mean and median intragastric pH, and percentage of time below pH 4. RESULTS: Eight foals were evaluated age 1-3 days, a gestational age of at least 320 days or reported to be full term. The mean (3.19 +/- 1.50 vs. 6.20 +/- 0.93) and median (4.6 +/- 1.7 vs. 6.86 +/- 0.89) pH were significantly higher and the percentage of time below pH 4 (32.25 vs. 1.1%) was significantly lower in the post treatment compared to the pretreatment period. CONCLUSION: Omeprazole paste effectively increases intragastric pH in clinically ill neonatal foals after one dose at 4 mg/kg bwt orally.     

The efficacy and pharmacokinetics of long-term low-level intraruminal administration of tricalbendazole in buffalo with induced fasciolosis

A study was conducted on the pharmacokinetics and therapeutic efficacy of triclabendazole at three low dose rates of 0.5, 1.0 and 1.5 mg/kg body weight in buffaloes experimentally infected with Fasciola gigantica. The pharmacokinetics were compared with the effects of a single intraruminal dose at 24.0 mg/kg body weight in uninfected buffaloes. At all three dose rates, an equilibrium between the absorption of triclabendazole and the disposition of its metabolites was observed by days 3 and 4 and remained almost unchanged thereafter. Continuous daily dosing at 1.5 mg/kg body weight proved to be efficacious against liver fluke infection in buffaloes.Abbreviations TCBZ triclabendazole - p.i. post-infection - HPLC high-performance liquid chromatography - TCBZ-SO triclabendazole sulphoxide - TCBZ-SO2 triclabendazole sulphone - C _max peak concentration in plasma - T _max time to reach C _max - AUC area under the concentration-time curve - t _1/2 elimination half-life - epg eggs per gram