Serodiagnosis of acute toxoplasmosis in macropods

The sera of 34 Australian macropods, the brains of which had been bioassayed for Toxoplasma gondii, were used to establish that a titre greater than 1/32 was significant for a direct agglutination test against toxoplasmosis. In addition, the concentration of 2-mercaptoethanol required to destroy the IgM fraction of macropod serum was confirmed in a modified direct agglutination test. To further validate the tests, the serological responses of three eastern grey kangaroos (Macropus giganteus) dosed orally with T. gondii oocysts and one M. giganteus injected with T. gondii cysts were studied. The tests were then used to investigate a diagnosis of acute toxoplasmosis in four Tasmanian pademelons (Thylogale billardierii) clinically suspected of acquiring toxoplasmosis naturally. One hundred and fifty-one Bennett's wallabies (Macropus rufogriseus rufogriseus) and 85 T. billardierii were also tested to determine the prevalence of acute toxoplasmosis of macropods in the wild. Four percent of M. r. rufogriseus and 1.2% of T. billardierii possessed T. gondii-specific IgM in their sera.     

The efficacy of mebendazole and praziquantel againstTaenia saginata cysticercosis in cattle

Approximately 50,000Taenia saginata eggs were given orally to bullocks. Ten weeks later, mebendazole or praziquantel was administered in the fodder in single or multiple doses. The animals were slaughtered at intervals after medication when the numbers and viability of cysticerci in various sites were recorded. Single doses of 5 mg/kg mebendazole or 10 mg/kg praziquantel had little effect on the viability of cysticerci. One single dose of 25 mg/kg or 10 daily doses of 5 mg/kg mebendazole had some effect. Praziquantel was completely effective against the viability of cysticerci in either one single dose of 100 mg/kg or 10 daily doses of 10 mg/kg.     

Prevalence of Toxoplasma gondii antibody in wild macropods

An enzyme-linked immunosorbent assay (ELISA) was developed to measure total antibody to Toxoplasma gondii in serum samples from macropods. The validity of the assay was established by comparing parasite isolation in mice for 17 Tasmanian pademelons (Thylogale billardierii) and 17 Bennett's wallabies (Macropus rufogriseus rufogriseus). The ELISA was then used to detect antibody against T. gondii in serum from 236 macropods, collected from 21 locations in Tasmania, including Flinders Island. Antibody against T. gondii was detected in 20 animals (15 T. billardierii and 5 M. rufogriseus). There was a significant (p less than 0.01) difference in possession of T. gondii antibodies between adult (greater than or equal to 1 year of age) Tasmanian pademelons and Bennett's wallabies.     

Oral clindamycin disposition after single and multiple doses in normal cats

Eighteen normal cats were randomly allocated into three treatment groups and dosed with clindamycin aqueous solution for 10 days at a dosage rate of: (1) 5.5 mg/kg b.i.d.; (2) 11 mg/kg b.i.d.; or (3) 22 mg/kg once daily. Serum disposition of clindamycin was determined after the first and last dose of clindamycin was given, and was analyzed using model-independent pharmacokinetics by both the trapezoidal rule method and the predictive equation method. Complete blood counts and clinical chemistries were determined before and after the study. The trapezoidal rule method produced similar mean results with much less variance than the predictive equation method. Mean residence time was longer (P less than 0.05) after the high dose (393 +/- 77 min) than after either the low or medium doses (276 +/- 51 and 274 +/- 45 min, respectively). Oral volume of distribution (Vd(ss)/F) after the high dose (3.06 +/- 0.92 l/kg) was larger (P less than 0.05) than that after the low or medium doses (1.62 +/- 0.30 and 1.76 +/- 0.53 l/kg, respectively). Oral Vd(ss)/F was significantly smaller (P less than 0.001) after the last dose than after the first dose when analyzed by treatment group. Significant (P less than 0.01) decreases in the leukogram and erythrogram were observed, due to the large amount of blood collected for drug analysis. No clinical signs of drug intoxication were observed, and no drug-related necropsy findings were found.     

Comparisons of different combinations of analogues of PGF2 alpha and dopamine agonists for the termination of pregnancy in dogs.

Groups of five pregnant bitches were treated to terminate the pregnancy with four combinations of drugs, starting 28 days after the estimated surge of luteinising hormone (LH), 22 to 28 days after the first mating. The treatments were: cabergoline administered orally for 10 days at a dose of 5 micrograms/kg and a single subcutaneous injection of 2.5 micrograms/kg cloprostenol at the start of the treatment; the same dose of cabergoline plus two doses of 1 microgram/kg cloprostenol administered on days 28 and 32 after the LH surge; bromocryptine administered orally at a dose of 30 micrograms/kg three times a day for 10 days plus a single dose of 2.5 micrograms/kg cloprostenol; the same dose of bromocryptine plus two doses of 1 microgram/kg cloprostenol; and a group of five pregnant bitches was left untreated. The pregnancies were terminated in all but one of the treated bitches, in each case by resorption of the fetuses. There were few side effects in the bitches treated with two doses of 1 microgram/kg cloprostenol, and were present but acceptable in those treated with one dose of 2.5 micrograms/kg. Plasma progesterone concentrations decreased to less than 1 ng/ml within 72 hours of the start of treatment and remained low except in the bitch in which pregnancy was not terminated. In the five untreated bitches, plasma progesterone remained high and they whelped normally. In the treated groups, the intervals between successive displays of oestrus were reduced by approximately 70 days in comparison with previous cycles or with the control group, but the fertility of the dogs was not affected adversely.     

Pharmacokinetics of pentoxifylline in dogs after oral and intravenous administration

OBJECTIVE: To evaluate the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl-metabolite, metabolite 1 (M1), in dogs after IV administration of a single dose and oral administration of multiple doses. ANIMALS: 7 sexually intact, female, mixed-breed dogs. PROCEDURE: A crossover study design was used so that each of the dogs received all treatments in random order. A drug-free period of 5 days was allowed between treatments. Treatments included IV administration of a single dose of PTX (15 mg/kg of body weight), oral administration of PTX with food at a dosage of 15 mg/kg (q 8 h) for 5 days, and oral administration of PTX without food at a dosage of 15 mg/kg (q 8 h) for 5 days. Blood samples were taken at 0.25, 0.5, 1, 1.5, 2, 2.5, and 3 hours after the first and last dose of PTX was administered PO, and at 5, 10, 20, 40, 80, and 160 minutes after PTX was administered IV. RESULTS: PTX was rapidly absorbed and eliminated after oral administration. Mean bioavailability after oral administration ranged from 15 to 32% among treatment groups and was not affected by the presence of food. Higher plasma PTX concentrations and apparent bioavailability were observed after oral administration of the first dose, compared with the last dose during the 5-day treatment regimens. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, oral administration of 15 mg of PTX/kg results in plasma concentrations similar to those produced by therapeutic doses in humans, and a three-times-a-day dosing regimen is the most appropriate.     

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.     

Curing experimental Bryophyllum tubiflorum poisoning of cattle with activated carbon, electrolyte replacement solution and antiarrhythmic drugs

A slurry of activated carbon (activated charcoal) in electrolyte replacement solution given by stomach tube and antiarrhythmic drugs given parenterally cured 9 of 11 calves dosed 7 to 24 h previously with a lethal amount (20g/kg) of Bryophyllum tubiflorum flower heads. Two of another 4 calves treated 26 to 36 h after dosing with flowers survived. B. tubiflorum toxins are bufadienolides (cardiac glycosides). Activated carbon was effective at a single dose of 5 g/kg. Calves were rehydrated with oral electrolyte replacement solution at 150 ml/kg in divided doses over 24 h. Tachycardia was treated with intravenous lignocaine (200 mg doses) or propranolol (5 mg doses) and atrioventricular block with atropine (0.5 mg/kg).     

The pharmacokinetics and pharmacodynamics of alfaxalone in cats after single and multiple intravenous administration of Alfaxan® at clinical and supraclinical doses

This study aimed to determine the pharmacokinetic parameters and pharmacodynamics of alfaxalone in a 2‐hydroxypropyl‐β‐cyclodextrin alfaxalone formulation (Alfaxan^®, Jurox Pty Ltd, Rutherford, NSW, Australia) in cats after single administration at clinical and supraclinical dose rates and as multiple maintenance doses. First, a prospective two‐period cross‐over study was conducted at single clinical and supraclinical doses. Second, a single group multiple dose study evaluated the effect of maintenance doses. Eight (five female and three male) domestic cats completed the cross‐over experiment and six female cats completed the multiple dose study. In the first experiment, alfaxalone was administered intravenously (IV) at 5 or 25 mg/kg with a washout period of 14 days. In the second experiment, alfaxalone was administered IV at 5 mg/kg followed by four doses each of 2 mg/kg, administered at onset of responsiveness to a noxious stimulus. Blood was collected at prescribed intervals and analysed by LCMS for plasma alfaxalone concentration. Noncompartmental pharmacokinetics were used to analyse the plasma alfaxalone data. The plasma clearance of alfaxalone at 5 and 25 mg/kg differed statistically at 25.1 and 14.8 mL/kg/min respectively. The elimination half lives were 45.2 and 76.6 min respectively. Alfaxalone has nonlinear pharmacokinetics in the cat. Nevertheless, for cats dosed with sequential maintenance doses, a regression line through their peak plasma concentrations indicated that there was no clinically relevant pharmacokinetic accumulation. The duration of nonresponsiveness after each maintenance dose was similar at approximately 6 min, indicating a lack of accumulation of pharmacodynamic effect. The cardiovascular and respiratory parameters measured in cats after administration of the labelled doses of Alfaxan^® were stable. In conclusion, the pharmacokinetics of alfaxalone in cats are nonlinear. At clinical dose rates, however, neither alfaxalone nor its effects accumulated to a clinically relevant extent. Further, in the un‐premedicated cat the induction and maintenance of surgical anaesthesia was free of untoward events after a dose of 5 mg alfaxalone/kg body weight followed by four sequential doses of 2 mg/kg as needed (i.e., approximately 7 to 8 mg/kg/h).     

Efficacy of levamisole alone and in combination with mebendazole against Gongylonema pulchrum infection in rabbits

Gongylonema pulchrum is an important parasite of captive primates. Twelve rabbits were infected with 30 third-stage larvae of G. pulchrum. At 4–7 months post-infection, animals were administered levamisole at a single dose of 12 mg/kg, levamisole at 8 mg/kg three times at 2-day intervals, levamisole at a single dose of 8 mg/kg after administration of mebendazole at 70 mg/kg for 3 days or 8 ml of distilled water for 3 days (control). Necropsy at 14 days after treatment revealed that single and multiple dosages of levamisole reduced nematode burdens by 68.4% and 89.5%, respectively. The combined regimen of mebendazole and levamisole exhibited high efficacy for treating G. pulchrum located widely within the upper digestive tract, with a reduction of 98.2%. These results suggest that this combined chemotherapy treatment may be effective against G. pulchrum infection, including buccal and lingual gongylonemiasis in primates.     

Ototoxic potential of gentamicin in ponies

Ototoxicosis was evaluated in 6 healthy ponies given 5 mg of gentamicin/kg of body weight, q 8 h, IM. Ponies 1, 2, and 3 were dosed for 7 days and ponies 4, 5, and 6 were dosed for 14 days. Serum peak and trough concentrations of gentamicin were measured by radioimmunoassay at regular intervals. Brain stem auditory-evoked responses were recorded every 5 days up to 60 days after the first dose to monitor auditory function. Although serum gentamicin concentrations were within or above the accepted clinical therapeutic range, loss of auditory function was not observed at the frequency range (1 to 4 kHz) tested. Serum chemical values remained within the accepted clinical range and no evidence of nephrotoxicosis was observed. Seemingly, gentamicin given IM to healthy ponies was safe and had minimal risk of side effects.     

Effect of intravenous dose escalation with alfaxalone and propofol on occurrence of apnoea in the dog

Spontaneous ventilation after induction of anaesthesia with intravenous alfaxalone or propofol was evaluated in a dose escalation study using 6 dogs. Each dog was dosed at 1×, 2×, 5×, 10× and 20× multiples of the labelled doses (2mg/kg for alfaxalone; 6.5mg/kg for propofol), until apnoea was observed. For each administration, the entire calculated dose was delivered over 1 min. All 6 dogs ventilated spontaneously after labelled (1×) doses of each drug but became apnoeic at 5× dose of propofol versus 20× dose of alfaxalone. For propofol at 2× and 5× doses, 4 and 0 dogs ventilated spontaneously respectively. For alfaxalone at 2×, 5× and 10× doses all 6, 4 and 1 dog ventilated spontaneously, respectively. The median dose which induced apnoea was higher for alfaxalone (5×) than for propofol (2×) (p=0.05). We concluded that induction of anaesthesia with propofol is more likely to induce apnoea than with alfaxalone.     

Plasma pharmacokinetics and muscle residue dynamics of mebendazole in Carassius auratus

Mebendazole is approved for use in aquatic animals and is widely used in Chinese aquaculture. We developed a pharmacokinetic and residue analysis for mebendazole levels in the goldfish (Carassius auratus). Plasma and muscle samples of C. auratus were taken after oral administration of 10 mg/kg mebendazole. The maximal drug plasma concentration of 0.55 mg/L was achieved at 48 hr and then declined with the elimination half‐life (T_1/2β) of 7.99 hr. Administration of 10 mg/kg by oral gavage for 5 successive days resulted in a peak mebendazole concentration of 0.70 mg/kg in muscle at 96 hr after the last dose. The drug was then eliminated at a relatively slow rate from muscle with T_1/2β of 68.41 hr. There was no detectable mebendazole in any muscle samples at 24 days postadministration. The AUC_last in plasma and muscle was 19.42 and 105.33 mg hr/L, respectively. These data provide information for dosage recommendations and withdrawal time determinations for mebendazole use in aquariums.     

The pharmacokinetics of maropitant citrate dosed orally to dogs at 2 mg/kg and 8 mg/kg once daily for 14 days consecutive days

The pharmacokinetics of maropitant were evaluated in beagle dogs dosed orally with Cerenia^® tablets (Pfizer Animal Health) once daily for 14 consecutive days at either 2 mg/kg or 8 mg/kg bodyweight. Noncompartmental pharmacokinetic analysis was performed on the plasma concentration data to measure the AUC_0–24 (after first and last doses), C_t (trough concentration—measured 24 h after each dose), C_max (after first and last doses), t_max (after first and last doses), λ_z (terminal disposition rate constant; after last dose), t_1/2 (after last dose), and CL/F (oral clearance; after last dose). Maropitant accumulation in plasma was substantially greater after fourteen daily 8 mg/kg doses than after fourteen daily 2 mg/kg doses as reflected in the AUC_0–24 accumulation ratio of 4.81 at 8 mg/kg and 2.46 at 2 mg/kg. This is most likely due to previously identified nonlinear pharmacokinetics of maropitant in which high doses (8 mg/kg) saturate the metabolic clearance mechanisms and delay drug elimination. To determine the time to reach steady‐state maropitant plasma levels, a nonlinear model was fit to the least squares (LS) means maropitant C_t values for each treatment group. Based on this model, 90% of steady‐state was determined to occur at approximately four doses for daily 2 mg/kg oral dosing and eight doses for daily 8 mg/kg oral dosing.     

Serum and tissue fluid norfloxacin concentrations after oral administration of the drug to healthy dogs

Norfloxacin, a 4-quinolone antibiotic, was administered orally to 4 healthy dogs at dosages of 11 and 22 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosing regimens. Serum and tissue cage fluid (TCF) norfloxacin concentrations were measured at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after the first and seventh dose of each dosing regimen. When administered at a dosage of 11 mg/kg, the mean peak serum concentration (Cmax) was 1.0 microgram/ml at 1 hour, the time of mean peak concentration (Tmax) after the first dose. After the seventh dose, the Cmax was 1.4 micrograms/ml at Tmax of 1.5 hours. The Tmax for the TCF concentration was 5 hours, with Cmax of 0.3 microgram/ml and 0.7 microgram/ml after the first and seventh dose, respectively. When administered at a dosage of 22 mg/kg, the serum Tmax was 2 hours after the first dose, with Cmax of 2.8 micrograms/ml. After the seventh dose, the serum Tmax was 1.5 hours, with Cmax of 2.8 micrograms/ml. The Tmax for the TCF concentration was 5 hours after the first and seventh doses, with Cmax of 1.2 micrograms/ml and 1.6 micrograms/ml, respectively. After the seventh dose, the serum elimination half-life was 6.3 hours for a dosage of 11 mg/kg and was 6.7 hours for a dosage of 22 mg/kg. For serum concentration, the area under the curve from 0 to 12 hours (AUC0----12) was 8.77 micrograms.h/ml and 18.27 micrograms.h/ml for dosages of 11 mg/kg and 22 mg/kg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of an oxfendazole pulsed release bolus for control of parasitic gastroenteritis in calves in a rotational grazing system

A group of 71 Friesian bullocks, aged six to nine months, vaccinated against lungworm, were randomly allocated on a liveweight basis to two groups of 40 and 31 animals. At turn-out each calf in the group of 40 calves was dosed orally with a pulsed release bolus designed to deliver five doses of oxfendazole at regular intervals during a period of up to 130 days, the first dose being released about 21 days after administration. The group treated with the bolus grazed 2.4 ha and the control group grazed 3.6 ha of permanent pasture for six weeks before having additional access to similar areas of silage aftermath. The control group was treated 99 days after turn-out and when they were housed with fenbendazole (7.5 mg/kg). Faecal worm egg counts, plasma pepsinogen activities, pasture larval counts and liveweights were recorded fortnightly. Significant reductions in worm egg counts and plasma pepsinogen activities were recorded in the calves dosed with the pulsed release bolus together with significant improvements in the liveweight of younger calves compared with control animals. Pasture larval counts were lower in the fields grazed by animals treated with the bolus.     

Nephrotoxicity in Goats Caused by Dosing with a Water Extract from the Stems of Narthecium Ossifragum Plants

Seven goats were given a single dose of an aqueous extract derived from 30 g (wet weight) of Narthecium ossifragum per kg liveweight. Their serum creatinine and urea concentrations increased to day 5 but then fell to normal by day 10. Serum magnesium increased to day 4 and decreased to normal by day 9. Their serum calcium concentration was lower than normal on days 4, 5 and 6. Histopathological examination of the kidneys of goats killed or found dead 2, 4, 6, 8, 11 or 16 days after dosing revealed tubular epithelial cell degeneration and necrosis. Regeneration of the tubular epithelium and signs of interstitial fibroplast proliferation and fibrosis could be seen in animals killed on days 8, 11, 16 and 42. No signs of liver damage were observed in 3 goats dosed with the insoluble plant material from 40 g (wet weight) Narthecium ossifragum per kg liveweight. The total dose was divided into three doses, which were given intraruminally within 7 h. The activities of aspartate aminotransferase, -glutamyl-transferase and glutamate dehydrogenase remained within the normal range in all 10 goats after dosing.     

Efficacy of albendazole for prevention of fascioliasis in sheep

Daily doses of albendazole administered as a premix in the feed for 35 days were effective in preventing Fasciola hepatica infections in 17 sheep in three groups: 5 mg/kg/day (6 sheep) was 100% effective; 3 mg/kg/day (5 sheep) was 98% effective; and 1 mg/kg/day (6 sheep) was 42% effective. Infective cysts were given daily for 5 days during the first week of treatment, treatment was continued an additional 28 days, and sheep were necropsied 14 weeks after final cyst inoculation. There were no visible lesions in any livers of sheep given albendazole at the rate of 5 mg/kg/day or in three of five livers of sheep dosed at the rate of 3 mg/kg/day. Sheep treated with albendazole had a mean weight gain of 2.7 kg, 4.0 kg, and 4.0 kg greater than the controls for the dosages of 1, 3, and 5 mg/kg/day, respectively. Determination of bile duct damage by measurement of serum gamma-glutamyl transpeptidase activity at 9 weeks after final cyst inoculation revealed increases of 3.0X, 1.0X, and 1.1X for the dosages of 1, 3, and 5 mg/kg/day, respectively, and 2.3X for the control, as compared with 7 weeks after final cyst inoculation.     

The susceptibility of two species of wallaby to infection with Trypanosoma evansi

OBJECTIVE: To determine the susceptibility of the agile wallaby (Macropus agilis) and the dusky pademelon (Thylogale brunil) to infection with Trypanosoma evansi. METHOD: Two agile wallabies and three dusky pademelons were experimentally infected with between 5 x 10(4) and 10 x 10(4) T evansi from a cryopreserved stabilate isolated from an indonesian buffalo. Animals were observed twice daily for clinical signs and blood was collected every 3 days to determine parasitaemia. Necropsy was conducted on animals that died or were euthanised when in extremis and representative tissue sections examined. RESULTS: All wallabies developed a high parasitaemia by 6 days after infection, which persisted until death or euthanasia in extremis, between days 8 and 61. Clinical signs included anorexia, weakness and ataxia. Anaemia occurred in one wallaby that survived for 61 days. Gross pathological changes varied between animals. They included pericarditis, serous atrophy of fat, splenomegaly, ulcerative gastritis and enteritis. Histological changes were characterised by a mononuclear cell infiltration of the connective tissue of most organs with little cellular destruction. Striking lesions were seen in the choroid, heart, stomach and small intestine. CONCLUSION: Agile wallabies and pademelons are highly susceptible to infection with T evansi. Wallabies, therefore, have the potential to spread T evansi within New Guinea and Australia if infection is introduced. Mortality is likely to be high thereby acting as an indicator of recent introduction. Histological changes seen in wallabies infected with T evansi are diagnostic for infections occurring in Australia and Papua New Guinea.     

Effects of different doses of dog-derived Sarcocystis sporocysts on growth rate and haematocrit in lambs

Four-week-old lambs at pasture were dosed with dog-derived Sarcocystis sporocysts. No difference in growth rates was apparent at a dose of 1 X 10(3) sporocysts per lamb. The minimum dose required to depress growth rate was 2.5 X 10(3) sporocysts per lamb: at 4 weeks post-inoculation (w.p.i.) the weight gain of lambs infected with this dose was 0.6 kg less than the non-infected controls (P less than 0.05). At 11 w.p.i. the difference was 0.7 kg, but this was not significant because of the greater average body weights of both groups. Lambs given 5 X 10(3) sporocysts showed significant depression of weight gain at both 4 and 11 w.p.i. Haematocrit levels at 4-5 weeks post-inoculation were depressed by doses as low as 1 X 10(3) sporocysts.