Effect of intraperitoneal inoculation of mebendazole on Taenia saginata cysticercosis in calves

Mebendazole was injected intraperitoneally at a dose of 40 mg/kg into six calves that had been inoculated 6 weeks earlier with eggs of T. saginata. The lethal effect of the drug on cysticerci was not significant in the mebendazole treated animals in comparison with those treated with a placebo. This was evaluated by counting the total number of cysticerci in each calf and the relative numbers of viable and degenerated cysts, an in vitro test for viability of cysticerci, and histological examination of the infected muscle tissue.     

Plasma concentrations of praziquantel after oral administration of single and multiple doses in loggerhead sea turtles (Caretta caretta)

OBJECTIVE: To determine the pharmacokinetics of praziquantel following single and multiple oral dosing in loggerhead sea turtles. ANIMALS: 12 healthy juvenile loggerhead sea turtles. PROCEDURE: Praziquantel was administered orally as a single dose (25 and 50 mg/kg) to 2 groups of turtles; a multiple-dose study was then performed in which 6 turtles received 3 doses of praziquantel (25 mg/kg, PO) at 3-hour intervals. Blood samples were collected from all turtles before and at intervals after drug administration for assessment of plasma praziquantel concentrations. Pharmacokinetic analyses included maximum observed plasma concentration (Cmax), time to maximum concentration (Tmax), area under the plasma praziquantel concentration-time curve, and mean residence time (MRTt). RESULTS: Large interanimal variability in plasma praziquantel concentrations was observed for all dosages. One turtle that received 50 mg of praziquantel/kg developed skin lesions within 48 hours of administration. After administration of 25 or 50 mg of praziquantel/kg, mean plasma concentrations were below the limit of quantification after 24 hours. In the multiple-dose group of turtles, mean plasma concentration was 90 ng/mL at the last sampling time-point (48 hours after the first of 3 doses). In the single-dose study, mean Cmax and Tmax with dose were not significantly different between doses. After administration of multiple doses of praziquantel, only MRTt was significantly increased, compared with values after administration of a single 25-mg dose. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of 25 mg of praziquantel/kg 3 times at 3-hour intervals may be appropriate for treatment of loggerhead sea turtles with spirorchidiasis.     

吡喹酮注射液对水牛血吸虫病的临床治疗效果

采用粪便毛蚴孵化法筛选自然感染血吸虫病水牛,考察30%吡喹酮注射液对水牛血吸虫病的临床治疗效果。在实验性临床试验中,将自然感染血吸虫病水牛随机分为5组,分别为吡喹酮注射液高（20 mg/kg）、中（10 mg/kg）、低（5 mg/kg）剂量组,吡喹酮片组（30 mg/kg）和阳性对照组（不用药组）。给药30 d后,吡喹酮注射液高、中、低剂量组及吡喹酮片组的粪便毛蚴孵化转阴率分别为100.0%、100.0%、77.8%和85.7%。在扩大临床试验中,将自然感染血吸虫病水牛随机分为2组,分别为吡喹酮注射液推荐剂量组（10 mg/kg）和吡喹酮片组（30 mg/kg）,给药30 d后,吡喹酮注射液组的52头患牛的粪便毛蚴孵化转阴率为100%,吡喹酮片组的6头患牛的粪便毛蚴孵化转阴率为100%。研究结果表明,30%吡喹酮注射液对水牛血吸虫病具有良好的治疗效果,给药方便,可以替代传统内服片剂,临床推荐剂量为10 mg/kg。     

Clinical Therapeutic Effect of Praziquantel Injection on Buffalo Schistosomiasis

To observe the clinical therapeutic effect of 30% praziquantel injection on buffalo schistosomiasis, the sick buffalos naturally infected with Schistosoma japonicum were selected by miracidium hatching method. In experimental clinical trials, sick buffalos were randomly divided into five groups, high-dose (20 mg/kg), middle-dose (10 mg/kg) and low-dose (5 mg/kg) praziquantel injection groups, praziquantel tablet group (30 mg/kg) and positive control group. After the treatment of 30 d, the negative conversion rate of miracidium were 100.0%, 100.0%, 77.8% and 85.7%, respectively, in praziquantel injection groups with the high, middle and low dose and oral medication group. In expanded clinical trials, the sick buffalos were randomly divided into two groups, praziquantel injection group (10 mg/kg, i.m.) and praziquantel tablet group (30 mg/kg). The results showed that, the negative conversion rate of miracidium were all 100% in the former 52 patients and the latter 6 patients after 30 d. The research confirmed that praziquantel injection was significantly effective in the treatment of buffalo schistosomiasis and convenient for administration. It was concluded that 30% praziquantel injection could replace the traditional oral praziquantel tablet for the treatment of buffalo schistosomiasis, and the recommended dose was 10 mg/kg.     

Pharmacokinetics of potassium bromide in adult horses

OBJECTIVE: To determine the pharmacokinetics of potassium bromide (KBr) in horses after single and multiple oral doses. ANIMALS: Twelve adult Standardbred and Thoroughbred mares. PROCEDURE: Horses were randomly assigned to two treatment groups. Group 1 horses were given a single oral dose of 120 mg/kg potassium bromide. Part 2 of the study evaluated a loading dose of 120 mg/kg KBr daily by stomach tube for 5 days, followed by 40 mg/kg daily in feed for 7 days. Serum concentrations of KBr were measured to construct concentration versus time curves and to calculate pharmacokinetic parameters. Treated horses were monitored twice daily by clinical examination. Serum concentrations of sodium, potassium and chloride ions and partial pressures of venous blood gases were determined. RESULTS: Maximum mean serum concentration following a single dose of KBr (120 mg/kg) was 423 +/- 22 microg/mL and the mean elimination half-life was 75 +/- 14 h. Repeated administration of a loading dose of KBr (120 mg/kg once daily for 5 d) gave a maximum serum concentration 1639 +/- 156 microg/mL. The administration of lower, maintenance doses (40 mg/kg once daily) was associated with decreased serum bromide concentrations, which plateaued at approximately 1000 microg/mL. Administration of KBr was associated with significant but transient changes in serum potassium and sodium concentrations, and possible changes in base excess and plasma bicarbonate concentrations. High serum concentrations of bromide were associated with an apparent increase in serum chloride concentrations, when measured on an ion specific electrode. CONCLUSIONS: and clinical relevance Loading doses of 120 mg/kg daily over 5 d and maintenance doses of approximately 90 mg/kg of KBr administered once daily resulted in serum bromide concentrations consistent with therapeutic efficacy for the management of seizures in other species. The clinical efficacy of this agent as an anticonvulsant medication and/or calmative in horses warrants further investigation.     

Histopathological and histoenzymatic studies on experimental Taenia saginata cysticercosis

In young Taenia saginata cysticerci the reactions for alkaline phosphatase (AlPh), acid phosphatase (AcPh), ATP-ases, succinic dehydrogenase (SDH) and lacto dehydrogenase (LDH) were mild. The reactions were concentrated in the walls of spiral canals (AlPh, SDH) and in the outer layer of the bladder (AlPh). The reactions were more intensive in older cysticerci. In these, the reaction of AlPh marked a network of blood vessels winding around the larva. In dying cysticerci the reactions for oxidative enzymes (SDH, LDH) were weaker but the activity of the hydrolytic enzymes (AlPh, AcPh) was increased. These findings suggest that histoenzymatic reactions may be helpful in determining the viability and the age of cysticerci. T. saginata cysticerci in sheep and goats provoked an early and intensive cellular reaction. The histopathological appearance of the cysticerci as they were destroyed in the abnormal hosts was similar to that of cysticerci localized in abnormal tissue of the natural host (e.g., lung of calves). Treatment with mebendazole caused an intensive infiltrative reaction against dying cysticerci and a degenerative process in the surrounding muscle tissue. The treatment with praziquantel provoked a weak infiltration around dead cysticerci and did not affect the muscle tissue. In both cases the remnants of T. saginata cysticerci disappeared very slowly.     

The effect of mebendazole on Echinococcus granulosus and Taenia hydatigena infections in dogs.

The effect of micronised mebendazole on Echinococcus granulosus and Taenia hydratigena has been investigated in a trial involving 175 dogs. The hydatid organism was eliminated from the dogs at dose rates of either 160 mg/kg given on one occasion or 20 mg/kg given on two occasions. A single dose of 20 mg/kg eliminated T hydratigena. The drug was readily accepted when given in food and there were no untoward sequelae.     

Toxic effects of mebendazole at high dose on the haematology of red-legged pademelons (Thylogale stigmatica)

OBJECTIVE: To investigate the effects of mebendazole at high dose on the haematology of macropods. Experimental. PROCEDURE: Five red-legged pademelons (Thylogale stigmatica) were dosed orally with mebendazole at 50 mg/kg/d for 5 to 6 days. Two control pademelons were dosed with water. Regular blood samples were taken for haematology over 20 days. RESULTS: All four treated pademelons sampled at 5 days developed severe leucopenia and neutropenia, moderate lymphopenia, thrombocytopenia, eosinopenia and monocytopenia, as well as bone marrow aplasia within 5 to 11 days after the first mebendazole dose. Four pademelons died unexpectedly or became ill and were euthanased 5 to 11 days after the first dose while the other animal recovered after 5 days of illness. Necropsy revealed systemic infection with opportunistic enteric bacteria, non-suppurative inflammation in tissues, haemorrhage and ulceration of the gastrointestinal tract. CONCLUSIONS: Red-legged pademelons rapidly develop bone-marrow aplasia and subsequent septicaemia after administration of high doses of mebendazole. Mebendazole at high doses should not be used for macropods.     

Effect of mebendazole on hydatid cysts in pigs

Mebendazole given per os was found to be effective against larval Echinococcus granulosus infection in pigs. Twenty-four pigs were experimentally inoculated with adult E. granulosus tapeworms. Mebendazole (40 mg/kg) or placebo was injected into six pigs 2 months after infection. Seven other pigs were given mebendazole (25 mg/kg) in their feed for 10 days twice (2 and 5 months after infection). Post-mortem examination performed 8 months after infection revealed that two of the pigs treated with mebendazole per os had a single hydatid cyst each; the other five pigs were free of infection. All eleven control untreated pigs were infected with between two and 21 cysts of E. granulosus.Mebendazole given intraperitoneally was not effective as mebendazole given per os in preventing the development of hydatid cysts in pigs.     

Pharmacokinetics of potassium bromide in adult horses

OBJECTIVE: To determine the pharmacokinetics of potassium bromide (KBr) in horses after a single and multiple oral doses. ANIMALS: Twelve adult Standardbred and Thoroughbred mares. PROCEDURE: Horses were randomly assigned into two treatment groups. In Part 1 of the study, horses were given a single oral dose of 120 mg/kg KBr. Part 2 of the study evaluated a loading dose of 120 mg/kg KBr daily by stomach tube for 5 days, followed by 40 mg/kg daily in feed for 7 days. Serum concentrations of bromide were determined by colorimetric spectrophotometry following drug administration to permit determination of concentration versus time curves from which pharmacokinetic parameters could be calculated. Treated horses were monitored twice daily by clinical examination. Serum concentrations of sodium, potassium and chloride ions and partial pressures of venous blood gases were determined. RESULTS: Maximum mean serum bromide concentration following a single dose of KBr (120 mg/kg) was 284 +/- 15 microg/mL and the mean elimination half-life was 75 +/- 14 h. Repeated administration of a loading dose of KBr (120 mg/kg once daily for 5 days) gave a maximum serum bromide concentration of 1098 +/- 105 microg/mL. The administration of lower, maintenance doses of KBr (40 mg/kg once daily) was associated with decreased serum bromide concentrations, which plateaued at approximately 700 microg/mL. Administration of KBr was associated with significant but transient changes in serum potassium and sodium concentrations, and possible changes in base excess and plasma bicarbonate concentrations. High serum concentrations of bromide were associated with an apparent increase in serum chloride concentrations, when measured on an ion specific electrode. CONCLUSIONS AND CLINICAL RELEVANCE: A loading dose of 120 mg/kg daily over 5 days and maintenance doses of approximately 90-100 mg/kg of KBr administered once daily are predicted to result in serum bromide concentrations consistent with therapeutic efficacy for the management of seizures in other species. The clinical efficacy of this agent as an anticonvulsant medication and/or calmative in horses warrants further investigation.     

Pharmacokinetic comparison of oral tablet and suspension formulations of grapiprant,a novel therapeutic for the pain and inflammation of osteoarthritis in dogs

A new anti‐inflammatory drug for pain (grapiprant) was recently shown to have minimal side effects following chronic (9‐month) daily oral dose of 6 or 50 mg/kg suspension. The current study compares the pharmacokinetics of the formulation used in the chronic safety study to those of the tablet formulation that will be marketed upon FDA approval. Sixteen Beagle dogs were randomized to receive single doses of either 6 or 50 mg/kg grapiprant as both suspension and table formulations within a cross‐over design with a 15‐day washout. Clinical observations were vomiting in one high‐dose suspension dog and loose stools in two dogs, one in each 6 mg/kg formulation group. For both formulations, grapiprant reached a maximum concentration within two hours. The tablet formulation had better bioavailability, with AUC_last values 34% higher at 6 mg/kg and 64% higher at 50 mg/kg compared to the suspension. Results on Day 0 were similar to those reported on Day 15, suggesting little to no accumulation. Using conversion factors of 1.34 and 1.64, these findings suggest that the 6 and 50 mg/kg suspension doses are equivalent to 4.5 and 30 mg/kg tableted doses, respectively. Combining these findings with the 9‐month safety study demonstrates that safety was evaluated at doses approximately 15‐fold above the demonstrated therapeutic dose of 2 mg/kg and 10‐fold over the ‘safety dose’, defined as the maximum dose a dog of any body weight could receive when dosed at 2 mg/kg with whole or half‐tablets.     

吡喹酮非水溶液注射剂的研制--日本血吸虫病治疗试验

利用本课题组研制的吡喹酮非水溶液注射剂，分别进行了小鼠和牛的日本血吸虫病治疗试验。结果表明，感染日本血吸虫的小鼠按每千克体质量20mg和30mg的剂量肌肉注射吡喹酮的减雌率均达100％，人工感染日本血吸虫的牛按每千克体质量10mg和12mg的剂量肌肉注射吡喹酮的减雌率均达100％，每千克体质量8mg的剂量的减雌率为96．41％。自然感染血吸虫病牛按每千克体质量10mg的剂量肌肉注射后30d，粪便转阴率达90．50％。这一结果说明，研制的吡喹酮注射剂具有良好的治疗效果。     

Synergistic action of mebendazole and levamisole in the treatment of a benzimidazole-resistant Haemonchus contortus in sheep

One-year old worm free, merino wethers, were each infected with 5000 H. contortus larvae of a strain resistant to mebendazole at a rate of 52 mg/kg body weight of sheep. After 21 days, they were assigned to two trials. The preliminary trial showed that mebendazole and levamisole acted synergistically on the H. contortus infection. In the second trial, sheep were treated with 0.35 mg/kg levamisole (one seventh the minimum effective dose against susceptible worms) or 40 mg/kg mebendazole (40 times the minimum effective dose against susceptible worms). In each case the anthelmintics did not reduce worm burdens, although mebendazole depressed egg production. However, when mebendazole and levamisole, at the above dose rates, were administered simultaneously, total worm counts in sheep were reduced by almost 60%. Similar results were obtained when the levamisole was administered 8 h or 14 h after mebendazole treatment. The implications of these observations for the treatment of benzimidazole-resistant haemonchiasis in sheep are discussed.     

Efficacy of amprolium for the treatment of pathogenic Eimeria species in Boer goat kids

This study evaluated the efficacy of two different doses of amprolium in goats heavily infected with pathogenic Eimeria species. Forty Boer goat kids ranging from 3 to 5 months of age with naturally occurring coccidiosis were randomly divided into 2 groups and treated orally with amprolium at doses of 10mg/kg daily for 5 days (n=20) or 50mg/kg daily for 5 days (n=20). The Eimeria oocyst per gram concentrations were significantly reduced on day 7 in the kids that received amprolium at 50mg/kg, however oocyst concentrations were not significantly reduced in goats that received the 10mg/kg dose. Out of 100 Eimeria oocysts identified from a pooled fecal sample, E. christenseni was the most frequently identified (52%) coccidial species present. The results of this trial indicate that amprolium can be an effective treatment for pathogenic Eimeria species in goat kids, however higher and extralabel doses (50mg/kg) should be used.     

Efficacy of two low-dose oral tylosin regimens in controlling the relapse of diarrhea in dogs with tylosin-responsive diarrhea: a prospective,single-blinded,two-arm parallel,clinical field trial

Background

Despite its wide acceptance as a treatment for canine chronic enteropathies, the macrolide antibiotic tylosin lacks official oral dosage recommendations. Not even textbooks share consensus about the dose; daily recommendations vary from 25 to 80 mg/kg and dosing intervals from one to three times daily.The objective of this prospective, single-blinded, two-arm parallel, clinical field trial was to determine whether doses of 5 mg/kg or 15 mg/kg tylosin administered orally once daily for seven days would have a similar effect on fecal consistency in diarrhea relapses to that of a 25 mg/kg dose of tylosin administered once daily for seven days, a dosage that has proved effective in controlling canine tylosin-responsive diarrhea (TRD). A further objective was to compare the efficacy of the 5 mg/kg and 15 mg/kg tylosin dosages. Fifteen client-owned dogs diagnosed with TRD that had responded to a dose of 25 mg/kg tylosin once daily for seven days were enrolled in the study. After a relapse of diarrhea the dogs were allocated into two groups receiving tylosin orally in doses of either 5 mg/kg or 15 mg/kg once daily for seven days. The owners were blinded to the dosage. The elimination of diarrhea was the main criterion in assessing treatment success. The mean fecal consistency score of the last three treatment days for all dosages, including 25 mg/kg, as evaluated by the owners according to a standardized fecal scoring system, served as the primary outcome measures.

Results

All eight dogs responded to the 5 mg/kg dose, and six of seven dogs responded to the 15 mg/kg dose. The mean fecal consistency scores at the 25 mg/kg tylosin dosage were no significantly different from scores at the 5 mg/kg or 15 mg/kg tylosin dosages (P = 0.672, P = 0.345).

Conclusions

Interestingly, 14/15 (93%) of the dogs responding to a dose of 25 mg/kg tylosin once daily for seven days also responded to the lower dosages at diarrhea relapse. The data indicate that a suitable dose of tylosin for treating diarrhea relapse in canine TRD could be as low as 5 mg/kg once daily for seven days.     

Uredofos: anthelmintic activity against nematodes and cestodes in dogs with naturally occurring infections.

A new broad-spectrum anthelmintic, uredofos, was tested in 146 dogs by single and multiple oral dosing. Single doses of 100 and 50 (but not 25) mg/kg were totally effective in removing Dipylidium caninum and Taenia spp from 46 dogs with infections of tapeworms. Among groups of 15 to 20 dogs, the average percentage efficacies against Toxocara canis for single soese of 100, 50, and 25 mg/kg were 98, 96, and 81%, respectively. The average percentage of efficacies against hookworm (Ancylostoma caninum) were greater than 96% in dogs treated with single doses of 100, 50, or 25 mg/kg and were 100% in the 35 dogs given 2 or 3 treatments (24-hour intervals) at dose levels of either 25 or 50 mg/kg. The whipworm, Trichuris vulpis, was not efficaciously eliminated by single doses of 25, 50, and 100 mg/kg (av percentage of efficacies of 30, 35, and 71%, respectively). Efficacy against T vulpis markedly improved when 2 doses were given at a 24-hour interval (av percentage of efficacies were 89% at dose level of 25 mg/kg and 99% at dose level of 50 mg/kg). At either dose (25 or 50 mg/kg), 3 daily treatments were no more efficacious against whipworms than were 2 doses. There was no evidence of drug toxicosis in any dogs tested. It was concluded that uredofos is highly effective against canine tapeworms, ascarids, and hookworms when given as a single dose of 50 mg/kg and against whipworm when given at dose level of 50 mg/kg/day for 2 days.     

芬苯达唑干混悬剂对绵羊裸头科绦虫的驱除效力试验

应用芬苯达唑干混悬剂,分别按5,10,20mg/kg体重剂量驱除绵羊裸头科绦虫,并设吡喹酮片剂20mg/kg体重剂量药物对照组和阳性对照组。粪检结果:芬苯达唑干混悬剂5,10,20mg/kg剂量对裸头科绦虫的粪便虫卵(节片)转阴率分别为70.0%、100.0%和100.0%。用药后14d剖检结果:芬苯达唑干混悬剂5mg/kg体重剂量对莫尼茨绦虫、无卵黄腺绦虫的驱虫率分别为70.7%、63.0%;10、20mg/kg体重剂量的驱虫率均达100.0%。结果表明10mg/kg和20mg/kg体重芬苯达唑干混悬剂试验剂量对绵羊裸头科2属绦虫均有效,其中10mg/kg以上剂量驱除绵羊裸头科绦虫高效安全。     

Dose-dependent pharmacokinetics of gentamicin in sheep

Dose-related changes in the pharmacokinetics of gentamicin sulfate were investigated in 9 sheep given 3, 10, or 20 mg/kg of body weight IV in a crossover design with a 24-day washout period. The pharmacokinetics of the 3 mg/kg single dose were compared with that of the terminal phase pharmacokinetics of 3 mg of gentamicin/kg IV every 8 hours for 7 days in 8 additional sheep. Serum concentrations were monitored for 21 to 24 days after the dose. Polyexponential equations were fit to each data set. The number of exponential terms was determined by optimizing the fit for each data set. The pharmacokinetics of the 3 mg/kg single dose were mainly described by triexponential equations. The 10 mg/kg and the 20 mg/kg single doses and the 3 mg/kg multiple-dose data were described by a tetraexponential equation. The elimination rate constant was significantly smaller (P less than 0.05) after the larger single doses, and the serum gentamicin clearance increased as the dose increased (P less than 0.05). The crossover design sequence had a significant effect on serum gentamicin clearance and the area under the curve normalized to unit dose (P less than 0.01). The final exponential phase was not detectable with the present assay sensitivity under the 3 mg/kg single dose. The triexponential equation underpredicted the terminal serum concentrations determined after the 3 mg/kg multiple dose, whereas the 4 phase equation overpredicted the same terminal serum concentrations, perhaps reflecting saturation of the tissue pools that were mirrored by the serum gentamicin concentrations after 24 hours. The present study emphasized the complexity of the terminal phase gentamicin. pharmacokinetics and acknowledged the need for a long-term washout period when using the crossover design for gentamicin pharmacokinetic studies.     

Field trial of praziquantel for control of fishborne zoonotic trematodes in reservoir hosts in Vietnam

This field trial was conducted to determine whether 40 or 75 mg/kg of praziquantel is suitable for treatment of fishborne zoonotic trematodes (FZT) in naturally infected dogs (n=10) and cats (n=11). Three days after treatment all animals at either dose were negative for small trematode eggs. In two cats and one dog treated with 75 mg/kg, however, a few damaged eggs were found 3 days post-treatment; no small trematode eggs were seen in these animals at day 14 post-treatment. In addition, at the 75 mg dose, two cats and two dogs experienced vomiting or diminished appetite. Therefore a praziquantel dose of 40 mg/kg is suggested for treatment of FZT in dogs and cats.     

Failure of oral zinc therapy to alleviate Bacteroides nodosus infections in cattle and sheep

Cattle and sheep with Bacteroides nodosus infection were treated orally with both high (65 mg Zn/kg and 82 mg Zn/kg) and low (1 mg Zn/kg and 8.6 mg Zn/kg) doses of zinc sulphate respectively. The lower dose rates administered weekly for one month, in the case of cattle, or daily for 2 weeks, in the case of sheep, had no effect either on serum zinc levels or the prevalence or severity of infection in treated animals. High dose rates of zinc (approximately 2.5 g Zn per head per day) were required to elevate serum levels above those normally present in both cattle and sheep. Even these dose rates continued daily for about 2 weeks had no beneficial effect on B. nodosus infection in either species.