Efficacy of injectable and pour-on microdose ivermectin in the treatment of goat warble fly infestation by Przhevalskiana silenus (Diptera, Oestridae)

The prophylactic efficacy of microdoses of injectable and pour-on ivermectin formulations against larval stages of Przhevalskiana silenus was assessed in naturally infected goats in the region of Calabria (southern Italy).Sixty-eight goats from two goat farms were divided into five groups: one group remained untreated, while the other four groups were treated with microdoses of ivermectin (5 and 10 microg/kg injectable formulation and 10 and 20 microg/kg pour-on formulation).The microdoses of ivermectin were fully effective in the treatment of goat warble fly infestation (GWFI) as no larvae emerged from the warbles in the treated groups, while all the larvae emerged in the control groups. Irrespective of the type of formulation used, the difference between the treated groups and the control group was statistically significant (P< 0.001). By contrast, no statistical differences were found between the goats treated with the injectable formulation and those receiving the pour-on applications, and between the two doses of the injectable and pour-on formulations used. Given the plasma concentrations it attains at its lowest dose (0.052 - 0.042 ng/ml for the injectable formulation and 0.030 ng/ml for the pour-on) the injectable formulation seems to offer the most reliable route for the administration of ivermectin microdoses and it is acceptable for milk consumption. The introduction of ivermectin in the early eighties and the use of microdoses in some cases have made it possible to control cattle hypodermosis in large areas of Europe. As with cattle hypodermosis, the administration of ivermectin microdoses in goats is particularly interesting because of the low costs involved and the low levels of residues found in goat milk; it may thus constitute the basis for GWFI control campaigns in areas where the disease is prevalent.     

Comparison of the efficacy of dermal formulations of ivermectin and levamisole for the treatment and prevention of Dictyocaulus viviparus infection in cattle

Four groups of six parasite-naive calves were infected at seven day intervals with three doses of infective larvae of Dictyocaulus viviparus. Twenty-one days after the first dose three of the groups were treated either with an injectable formulation of ivermectin at a dose rate of 200 micrograms/kg bodyweight, or with pour-on preparations of levamisole at 10 mg/kg or ivermectin at 500 micrograms/kg. On day 28 two calves from each group were slaughtered and their burdens of lungworms counted. On day 35 the remaining calves were reinfected with D viviparus infective larvae at a rate of 80 L3/kg. The levamisole preparation was 94.6 per cent effective and both ivermectin preparations were 100 per cent effective against the initial infections. The ivermectin-treated calves were protected from the reinfection which subsequently became patent in the levamisole-treated and control calves.     

Comparative plasma dispositions of ivermectin and doramectin following subcutaneous and oral administration in dogs

This study evaluates the comparative plasma dispositions of ivermectin (IVM) and doramectin (DRM) following oral and subcutaneous administration (200 microg/kg) over a 40-day period in dogs. Twenty bitches were allocated by weight in to four groups (Groups I-IV) of five animals each. Animals in the first two groups (Groups I and II) received orally the injectable solutions of IVM and DRM, respectively, at the dose of 200 microg/kg bodyweight. The other two groups (Groups III and IV) received subcutaneously injectable solutions at the same dose rate. Blood samples were collected between 1h and 40 days after treatment and the plasma samples were analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The results indicated that IVM produced a significantly higher maximum plasma concentration (C(max): 116.80+/-10.79 ng/ml) with slower absorption (t(max): 0.23+/-0.09 day) and larger area under the concentration versus time curve (AUC: 236.79+/-41.45 ng day/ml) as compared with DRM (C(max): 86.47+/-19.80 ng/ml, t(max): 0.12+/-0.05 day, AUC: 183.48+/-13.17 ng day/ml) following oral administration of both drugs; whereas no significant differences were observed on the pharmacokinetic parameters between IVM and DRM after subcutaneous administrations. In addition, subcutaneously given IVM and DRM presented a significantly lower maximum plasma concentration (C(max): 66.80+/-9.67 ng/ml and 54.78+/-11.99 ng/ml, respectively) with slower absorption (t(max): 1.40+/-1.00 day and 1.70+/-0.76 day, respectively) and larger area under the concentration versus time curve (AUC: 349.18+/-47.79 ng day/ml and 292.10+/-78.76 ng day/ml, respectively) as compared with the oral administration of IVM and DRM, respectively. No difference was observed for the terminal half-lives ((t(1/2lambda(z)) and mean residence times (MRT) of both molecules. Considering the pharmacokinetic parameters, IVM and DRM could be used by the oral or subcutaneous route for the control of parasitic infection in dogs.     

Pharmacokinetics of oral omeprazole in llamas

Gastrogard, an oral formulation of omeprazole, was given to six llamas at a dose of 4 mg/kg once a day for 6 days. Plasma samples were collected at 0, 15, 30, 45, and 60 min and 2, 3, 4, 6, 8, 12, and 24 h on days 1 and 6. Plasma omeprazole concentrations were measured by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters calculated included the area under the curve (AUC(0-infinity)), peak plasma concentration (Cmax), time of peak plasma concentration (Tmax), and terminal half-life (t(1/2)). On day 6, plasma omeprazole concentrations reached a Cmax of 0.12 microg/mL at a Tmax of 45 min. The t(1/2) of omeprazole was 2.3 h and the AUC(0-infinity) was 0.38 h x microg/mL. Plasma concentrations remained above the minimum concentration for inhibition of gastric acid secretion projected from other studies on day 6 in all the llamas for approximately 6 h. However, the AUC(0-infinity) was below the concentrations associated with clinical efficacy. It was not possible to measure oral systemic bioavailability because there was no i.v. data collected from these animals. However, using data published on the i.v. pharmacokinetics of omeprazole in llamas, oral absorption was estimated to be only 2.95%. Due to low absorption the oral dose was increased to 8 and 12 mg/kg and studies were repeated. There were no significant differences in Cmax, Tmax, or AUC(0-infinity) for either of the increased doses. These results indicate that after 6 days of treatment with doses up to 12 mg/kg, oral omeprazole produced plasma drug concentrations which are not likely to be associated with clinical efficacy in camelids.     

A comparative kinetic study of ivermectin and moxidectin in lactating camels (Camelus dromedarius).

The plasma and milk kinetics of ivermectin (IVM) and moxidectin (MXD) was evaluated in lactating camels treated subcutaneously (0.2 mg kg(-1)) with commercially available formulations for cattle. Blood and milk samples were taken concurrently at predetermined times from 12 h up to 60 days post-administration. No differences were observed between plasma and milk kinetics of IVM, while substantial differences were noted between plasma and milk profiles of MXD in that both the maximal concentration (Cmax) and the area under concentrations curves (AUC) were three to four-fold higher for milk than for plasma. The time (Tmax) to reach Cmax was significantly faster for MXD (1.0 day) than that for IVM (12.33 days). The Cmax and the AUC were significantly higher for MXD (Cmax = 8.33 ng ml(-1); AUC = 70.63 ng day ml(-1)) than for IVM (Cmax = 1.79 ng ml(-1); AUC = 30.12 ng day ml(-1)) respectively. Drug appearance in milk was also more rapid for MXD (Tmax = 3.66 days) compared to IVM (Tmax = 17.33 days). The extent of drug exchange from blood to milk, expressed by the AUCmilk/AUCplasma ratio, was more than three-fold greater for MXD (4.10) compared to that of IVM (1.26), which is consistent with the more lipophilic characteristic of MXD. However, the mean residence time (MRT) was similar in both plasma and milk for each drug.     

Pharmacokinetics of a novel formulation of ivermectin after administration to goats

OBJECTIVE: To evaluate the pharmacokinetics of a novel commercial formulation of ivermectin after administration to goats. ANIMALS: 6 healthy adult goats. PROCEDURE: Ivermectin (200 microg/kg) was initially administered IV to each goat, and plasma samples were obtained for 36 days. After a washout period of 3 weeks, each goat received a novel commercial formulation of ivermectin (200 microg/kg) by SC injection. Plasma samples were then obtained for 42 days. Drug concentrations were quantified by use of high-performance liquid chromatography with fluorescence detection. RESULTS: Pharmacokinetics of ivermectin after IV administration were best described by a 2-compartment open model; values for main compartmental variables included volume of distribution at a steady state (9.94 L/kg), clearance (1.54 L/kg/d), and area under the plasma concentration-time curve (AUC; 143 [ng x d]/mL). Values for the noncompartmental variables included mean residence time (7.37 days), AUC (153 [ng x d]/mL), and clearance (1.43 L/kg/d). After SC administration, noncompartmental pharmacokinetic analysis was conducted. Values of the variables calculated by use of this method included maximum plasma concentration (Cmax; 21.8 ng/mL), time to reach Cmax (3 days), and bioavailability (F; 91.8%). CONCLUSIONS AND CLINICAL RELEVANCE: The commercial formulation used in this study is a good option to consider when administering ivermectin to goats because of the high absorption, which is characterized by high values of F. In addition, the values of Cmax and time to reach Cmax are higher than those reported by other investigators who used other routes of administration.     

Plasma pharmacokinetics and faecal excretion of ivermectin, doramectin and moxidectin following oral administration in horses

The present study was carried out to investigate whether the pharmacokinetics of avermectins or a milbemycin could explain their known or predicted efficacy in the horse. The avermectins, ivermectin (IVM) and doramectin (DRM), and the milbemycin, moxidectin (MXD), were each administered orally to horses at 200 microg/kg bwt. Blood and faecal samples were collected at predetermined times over 80 days (197 days for MXD) and 30 days, respectively, and plasma pharmacokinetics and faecal excretion determined. Maximum plasma concentrations (Cmax) (IVM: 21.4 ng/ml; DRM: 21.3 ng/ml; MXD: 30.1 ng/ml) were obtained at (tmax) 7.9 h (IVM), 8 h (DRM) and 7.9 h (MXD). The area under the concentration time curve (AUC) of MXD (92.8 ng x day/ml) was significantly larger than that of IVM (46.1 ng x day/ml) but not of DRM (53.3 ng x day/ml) and mean residence time of MXD (17.5 days) was significantly longer than that of either avermectin, while that of DRM (3 days) was significantly longer than that of IVM (2:3 days). The highest (dry weight) faecal concentrations (IVM: 19.5 microg/g; DRM: 20.5 microg/g; MXD: 16.6 microg/g) were detected at 24 h for all molecules and each compound was detected (> or = 0.05 microg/g) in faeces between 8 h and 8 days following administration. The avermectins and milbemycin with longer residence times may have extended prophylactic activity in horses and may be more effective against emerging and maturing cyathostomes during therapy. This will be dependent upon the relative potency of the drugs and should be confirmed in efficacy studies.     

Pharmacokinetics of Eprinomectin in Plasma and Milk following Subcutaneous Administration to Lactating Dairy Cattle

Eprinomectin is only available as a topically applied anthelmintic for dairy cattle. To determine whether eprinomectin can be applied as an injectable formulation in dairy cattle, a novel injectable formulation was developed and was subcutaneously delivered to four lactating dairy cattle at a dose rate of 0.2 mg/ kg. Plasma and milk samples were collected. The concentrations of eprinomectin in all samples were determined by HPLC. The peak plasma concentration (C_max)of 44.0±24.2 ng/ml occurred 39±19.3 h after subcutaneous administration, equivalent to the C_max (43.76±18.23 ng/ml) previously reported for dairy cattle after a pour-on administration of 0.5 mg/kg eprinomectin. The area under the plasma concentration–time curve (AUC) after subcutaneous administration was 7354±1861 (ng h)/ml, higher than that obtained after pour-on delivery (5737.68±412.80 (ng h)/ml). The mean residence time (MRT) of the drug in plasma was 211±55.2 h. Eprinomectin was detected in the milk at the second sampling time. The concentration of drug in milk was parallel to that in plasma, with a milk to plasma ratio of 0.16±0.01. The highest detected concentration of eprinomectin in milk was 9.0 ng/ml, below the maximum residue limit (MRL) of eprinomectin in milk established by the Joint FAO/WHO Expert Committee on Food Additives in 2000. The amount of eprinomectin recovered in the milk during this trial was 0.39%±0.08% of the total administered dose. This study demonstrates that subcutaneous administration of eprinomectin led to higher bioavailability and a lower dose than a pour-on application, and that an injectable formulation of eprinomectin may be applied in dairy cattle with a zero withdrawal period.     

Duration of Anthelmintic Effect of Three Formulations of Ivermectin (Oral,Injectable and Pour-on) Against Multiple Anthelmintic-Resistant <Emphasis Type="Italic">Haemonchus contortus</Emphasis> in Sheep

We report the results of investigations that were conducted in a sheep flock in Uttaranchal, India where repeated failure of anthelmintic medication was noted. The study revealed that Haemonchus contortus in sheep had developed resistance to benzimidazoles (fenbendazole, mebendazole and albendazole), imidazothiazole (levamisole) and salicylanide (rafoxanide), while it was fully susceptible to avermectins (ivermectin). Further, the suppression of nematode egg output in faeces of sheep naturally infected with multiple anthelmintic-resistant H. contortus following treatment with ivermectin tablet (0.4 mg/kg body weight (bw), orally), ivermectin injection (1% w/v, 0.2 mg/kg bw, subcutaneously) and ivermectin pour-on (0.5 w/v, 0.5 mg/kg bw) was also studied over a period of 10 weeks post treatment. It was noted that ivermectin tablet after initial clearance of infection (faecal egg count reduction 100%), could not prevent establishment of new patent natural infection for even a single day, while ivermectin pour-on and injection prevented the establishment of new infection for 7 and 14 days post treatment, respectively. Maximum protection period (duration for which mean faecal egg count of sheep reaches 500 eggs per gram of faeces or more) of 68 days was recorded in sheep treated with injectable ivermectin, followed by pour-on (60 days) and oral (53 days) preparations.     

Comparison of the persistent efficacy of the injectable and pour-on formulations of doramectin against artificially-induced infection with Dictyocaulus viviparus in cattle

The persistent efficacy of the injectable and topical formulations of doramectin was compared against experimental challenges with infective larvae of Dictyocaulus viviparus in two separate studies. Four groups of 10 randomly-assigned calves, negative for lungworm larvae by the Baermann technique, were used in each study. Calves were treated subcutaneously in the midline of the neck or poured down the midline of the back with saline (1 ml/50 kg. injection: 1 ml/10 kg. pour-on) on Day 0 or doramectin (200 microg/kg = 1 ml/50 kg. injection: 500 microg/kg = 1 ml/10 kg. pour-on) on Day 0, 7, or 14. Two additional calves from the same pool of animals were randomly assigned as larval-viability monitors and received no treatment. Calves were inoculated daily with a gavage of approximately 100 larvae of D. viviparus from days 35 to 49 for the injectable study and days 28 to 42 for the pour-on study. The two larval viability monitor calves received approximately 3000 infective larvae in the same manner on Day 49 or 42 for the injectable and pour-on studies, respectively. Equal numbers of calves from each treatment group as well as the larval viability monitor calves were necropsied on days 14 and 15 after the last lungworm inoculation to enumerate the worm burden. The worms recovered were quantified and identified. For each study, geometric mean worm recoveries for each treatment group were back transformed from the natural log-transformed data (worm count +1) and were used to estimate percentage reduction. Doramectin injectable solution was 100.0% efficacious against lungworms for up to 49 days and the pour-on formulation was 100.0%, 93.1% and 81.5% effective in reducing lungworm infection resulting from challenge infection for up to 28, 35, and 42 days post-treatment, respectively.     

Pharmacokinetics of ivermectin in the yak (Bos grunniens)

The yak (Bos grunniens) belongs to the cattle family Bovidae and lives in the mountains of China and adjacent areas. Due to the physiological adaptations of yak to its environment and the lack of data, the ivermectin pharmacokinetic was studied following a single subcutaneous dose at the recommended dose for cattle (0.2 mg kg(-1)). The observed peak plasma concentration (Cmax) was 48.93 ng ml(-1) and the time to reach Cmax (Tmax) was 0.73 day. These results show a faster rate of absorption than in cattle. The values for the absorption half-life (t(1/2a)), the distribution half-life (t(1/2alpha)) and the terminal half-life (t(1/2beta)) were 0.31, 0.74 and 4.82 days, respectively. The calculated area under the concentration-time curve (AUC) was 146.2 ng day ml(-1) and the mean residence time (MRT) was 3.57 days. The availability of ivermectin appears low in yaks in comparison to cattle but equivalent to that reported in horses and is likely to be due to physiological characteristics of this species.     

Efficacy of eprinomectin pour-on against gastrointestinal nematodes and the nasal bot fly (Oestrus ovis) in sheep

The efficacy of the pour-on formulation of eprinomectin, at a dose rate of 0.5 mg/kg bodyweight, was assessed in sheep against three main species of gastrointestinal nematodes and against the nasal bot fly, Oestrus ovis, and some pharmacokinetic parameters were determined for 21 days after the treatment. By comparison with untreated control sheep, infected experimentally with Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis, eprinomectin was 100 per cent effective against the two abomasal species and 99.5 per cent effective against T. colubriformis. In ewes naturally infected with the nasal bot fly, the efficacy of the drug against O. ovis was 97.7 per cent. The mean (se) systemic area under the curve (AUC) was 56.0 (26.2) ng/day/ml and the mean residence time was 5.3 (1.0) days, but there were wide variations between individual sheep.     

Persistence of ivermectin in plasma and faeces following administration of a sustained-release bolus to cattle

Six calves (weight 210 to 230 kg) were dosed with an intra-ruminal slow-release bolus prepared to deliver ivermectin at a low daily dosage for 135 days. Ivermectin concentrations in jugular blood 160 days post-treatment were determined by high performance liquid chromatography (HPLC) using fluorescence detection. Ivermectin plasma concentrations increased gradually to achieve the steady-state concentration (20 ng ml(-1)) at approximately four days post-treatment, which was maintained for 120 days. The ivermectin peak plasma concentration (28.5 ng ml(-1)) was attained at 15 days post-administration of the bolus. The faecal ivermectin concentration rose to a maximal concentration of 4.1 microg g(-1) at four days post-treatment, dropping to a steady-state concentration of around 1.18 microg g(-1) which was maintained up to 120 days post-treatment. Ivermectin was detected in both plasma (0.05 ng ml(-1)) and faeces (2.67 ng g(-1)) up to 160 days. The high levels of ivermectin recovered in faeces indicate that a large proportion of the dose released by the bolus (80 to 90 per cent) is excreted in faeces.     

Pharmacokinetics of enrofloxacin administered intravenously and orally to foals

OBJECTIVE: To determine the pharmacokinetics of enrofloxacin administered IV and orally to foals. ANIMALS: 5 clinically normal foals. PROCEDURE: A 2-dose cross-over trial with IV and oral administration was performed. Enrofloxacin was administered once IV (5 mg/kg of body weight) to 1-week-old foals, followed by 1 oral administration (10 mg/kg) after a 7-day washout period. Blood samples were collected for 48 hours after the single dose IV and oral administrations and analyzed for plasma enrofloxacin and ciprofloxacin concentrations by use of high-performance liquid chromatography. RESULTS: For IV administration, mean +/- SD total area under the curve (AUC0-infinity) was 48.54 +/- 10.46 microg x h/ml, clearance was 103.72 +/- 0.06 ml/kg/h, half-life (t1/2beta) was 17.10 +/- 0.09 hours, and apparent volume of distribution was 2.49 +/- 0.43 L/kg. For oral administration, AUC0-infinity was 58.47 +/- 16.37 microg x h/ml, t1/2beta was 18.39 +/- 0.06 hours, maximum concentration (Cmax) was 2.12 +/- 00.51 microg/ml, time to Cmax was 2.20 +/- 2.17 hours, mean absorption time was 2.09 +/- 0.51 hours, and bioavailability was 42 +/- 0.42%. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with adult horses given 5 mg of enrofloxacin/kg IV, foals have higher AUC0-infinity, longer t1/2beta, and lower clearance. Concentration of ciprofloxacin was negligible. Using a target Cmax to minimum inhibitory concentration ratio of 1:8 to 1:10, computer modeling suggests that 2.5 to 10 mg of enrofloxacin/kg administered every 24 hours would be effective in foals, depending on minimum inhibitory concentration of the pathogen.     

Clinical and pharmacological properties of ivermectin in rabbits and guinea pigs.

When 400 micrograms ivermectin/kg was administered subcutaneously to rabbits infected with the ear mite Psoroptes cuniculi it significantly reduced the clinical score, and when 500 micrograms ivermectin/kg was administered subcutaneously to guinea pigs with mange due to Trixacaurus caviae it resulted in a clinical cure. In rabbits a subcutaneous dose of 400 micrograms/kg produced high and sustained concentrations of ivermectin in the tissues and body fluids for at least 13 days and its rate of depletion from tissues was similar to that observed in sheep and rats. The mean (+/- sem) maximum concentration in plasma was 42.0 +/- 9.7 ng/ml 37.2 +/- 5.0 hours after administration and the area under the concentration-time curve was 3543 +/- 580 ng/ml hours. After the administration of 500 micrograms ivermectin/kg to guinea pigs orally, subcutaneously or topically the drug could be detected in the plasma only after subcutaneous administration. The mean concentration 72 hours after its administration to four guinea pigs was 0.7 +/- 0.3 ng/ml.     

A non-arthropathic dose and its disposition following repeated oral administration of ofloxacin, a new quinolone antimicrobial agent, to juvenile dogs

A non-arthropathic dose and disposition of ofloxacin, a potent new quinolone antimicrobial agent, were assessed in male juvenile (3-month-old) dogs, when administered orally at 5, 10 and 20 mg/kg/day once daily for 8 consecutive days. Ofloxacin concentrations in sera and articular cartilages were analyzed by high-performance liquid chromatography (HPLC). Macroscopically, arthropathy characterized by fluid-filled vesicles in articular surface of the humerus and femur was observed in animals receiving 10 and 20 mg/kg/day of ofloxacin, but not in those given 5 mg/kg/day. At 20 mg/kg/day, arthropathy of comparable severity also occurred on day 2. Microscopically, the cavity formation in the middle zone of the articular cartilage was first identified and then necrotic chondrocytes were found numerous around the cavity, followed by appearance of chondrocyte clusters. In pharmacokinetics, peak serum concentration (Cmax) and area under the concentrations (AUC0-24) were increased in a dose-dependent manner. However, no remarkable differences in these two parameters were noted between a single and repeated treatments, suggesting no accumulation of the drug. The articular ofloxacin concentration 2 hr after treatment was approximately 1.8 (day 2) to 2.0 times (day 8) higher than the serum concentration. Based on these results, a non-arthropathic dose of ofloxacin in male juvenile dogs following an 8-day treatment is considered to be 5 mg/kg/ day, and its Cmax, AUC0-24 and articular cartilage concentrations 2 hr after treatment were 3.4 microg/ml, 35.1 microg-hr/m/ and 7.0 microg/g, respectively, under these experimental conditions. Thus, arthropathy due to ofloxacin may be predicted by monitoring serum drug concentration.     

Disposition of sulfadimethoxine in male llamas (Llama glama) after single intravenous and oral administrations.

This study determined the disposition of sulfadimethoxine in six, healthy, adult, gelded male llamas (Llama glama) by using a nonrandomized crossover design with i.v. dosing (58.8 +/- 3.0 mg/kg based on metabolic scaling) followed by oral dosing (59.3 mg/kg +/- 8.3). Blood samples were collected intermittently for a 72-hr period, and serum sulfadimethoxine concentrations were quantified using high-performance liquid chromatography. Serum sulfadimethoxine concentrations across time were subjected to standard pharmacokinetic analysis based on linear regression. Mean maximum serum concentration after oral dosing was 23.6 +/- 14.9 microg/ml, and extrapolated peak concentration after i.v. administration was 246.6 +/- 15.8 microg/ml. Total clearance of sulfadimethoxine was 45.4 +/- 13.9 L/kg. Half-lives after i.v. and oral administration were 541 +/- 111 min and 642.4 +/- 204.8 min, respectively. Oral bioavailability was 52.6 +/- 15%. These data suggest that the oral dose administered to llamas in this study, based on metabolic scaling from cattle, may be inadequate when compared with the reported minimum inhibitory concentration (512 microg/ml) breakpoint for sulfadimethoxine.     

The comparative serum disposition kinetics of subcutaneous administration of doramectin, ivermectin and moxidectin in the Australian Merino sheep

This study evaluates the comparative serum disposition kinetics of injectable formulations of doramectin (DRM), ivermectin (IVM) and moxidectin (MXD) in Australian Merino sheep. Thirty-six, 2-year-old sheep were allocated by weight into six groups of six animals. Animals in each group received 200 microg/kg of DRM, MXD, IVM or a combination of two of these drugs by subcutaneous (s.c.) injection. Blood was collected at designated intervals (between 1 h and 40 days after treatment) and the serum analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The results indicated that MXD administration produced a significantly higher maximum serum concentration and a more rapid absorption as compared with DRM and IVM. MXD and DRM had a significantly larger area under the concentration vs. time curve (AUC) than IVM, suggesting a more persistent effect for the former two products in sheep. The AUC for DRM was significantly higher when administered alone as compared with that observed when given in combination with MXD or IVM, suggesting preferential elimination of DRM compared with IVM and MXD from concurrent s.c. administration.     

Assessment of serum concentrations and sedative effects of fentanyl after transdermal administration at three dosages in healthy llamas

OBJECTIVE: To determine the serum concentrations and sedative effects of fentanyl after transdermal administration at 3 dosages in llamas. ANIMALS: 9 healthy adult female llamas (mean age, 8 +/- 3 years; mean weight, 150 +/- 18 kg). PROCEDURE: Llamas were allocated to 1 of 3 groups (3 llamas/group). Fentanyl patches (each providing transdermal delivery of 75 microg of fentanyl/h) were placed on shaved areas of the antebrachium of all llamas. In group 1, llamas were treated with 1 patch (anticipated fentanyl dosage, 75 microg/h). In group 2, llamas were treated with 2 patches (anticipated fentanyl dosage, 150 microg/h). In group 3, llamas were treated with 4 patches (anticipated fentanyl dosage, 300 microg/h). For each llama, the degree of sedation was assessed by use of a subjective scoring system and a blood sample was collected for determination of serum fentanyl concentration at 12, 24, 36, 48, 60, and 72 hours after patch placement. RESULTS: Following the placement of 4 patches, mean +/- SD serum fentanyl concentration in group 3 llamas reached 0.3 +/- 0.08 ng/mL within 12 hours. This concentration was sustained for 72 hours. In group 2, application of 2 patches provided inconsistent results; in group 1, application of 1 patch rarely provided measurable serum fentanyl concentrations. No llamas became sedated at any time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that application of four 75 microg/h fentanyl patches provides consistent, sustained serum fentanyl concentrations without sedation in llamas. However, the serum concentration of fentanyl that provides analgesia in llamas is not known.     

Efficacy of an oxibendazole-trichlorfon paste formulation against third stage larvae of Gasterophilus intestinalis and its safety in horses

A paste formulation containing 14.3 per cent of oxibendazole and 44 per cent of trichlorfon was administered to 33 ponies and horses. The dose rate used was equivalent to 10 mg and 30 mg/kg bodyweight, of oxibendazole and trichlorfon respectively. After treatment 25 animals passed between one and 82 third stage larvae of Gasterophilus intestinalis in their faeces. Dosing with 0.2 mg ivermectin/kg bodyweight three weeks later resulted in six animals expelling between one and four bots. The efficacy of the oxibendazole-trichlorfon paste was on average 96.2 per cent. This drug combination given to 52 ponies and horses at the indicated dose rate and to six ponies at twice that dose was tolerated without side effects except transient softening of the faeces in several animals and mild symptoms of colic in two horses.