Bioavailability of sulfamethoxypyridazine following intramuscular or subcutaneous administration in goats.

The pharmacokinetics of sulfamethoxypyridazine (SMP) was investigated in goats after a single intramuscular (im) or subcutaneous (sc) administration (100 mg/kg body weight). The biological half lives of SMP following im and sc administration were found to be 11.0 and 13.7 h, respectively. The systemic availabilities of the drug were calculated to be 68.6 and 58.7% following im and sc injections, respectively. The rapidity of absorption, almost similar availability, comparatively longer biological half-life and ease of administration suggest that the sc route of administration might be preferred over the im route. To achieve and maintain serum concentrations 25 micrograms/mL, a rational dosage regimen of SMP for goats would be 55 and 38 mg/kg body weight as the loading and maintenance doses, respectively, with a dosage interval of 24 h by the sc route.

Comparative pharmacokinetics of amikacin following a single intramuscular or subcutaneous administration in goats (Capra hircus).

The pharmacokinetics of amikacin sulfate was investigated following a single intramuscular (i.m.) or subcutaneous (s.c.) administration (10 mg/kg). The plasma concentration versus time data were analysed using the biexponential equation for first-order absorption and elimination phases for both the i.m. and s.c. routes. The absorption half life values for the i.m. and s.c. routes were found to be 14.64 and 12.36 min, respectively. The biological half-life values of amikacin following i.m. and s.c. routes were found to be 84.46 and 93.96 min, respectively. The systemic availability of amikacin for both the i.m. (102.15 +/- 5.08%) and s.c. (106.82 +/- 12.95%) routes was found to be almost complete. Thus, based on the data of short absorption half life, almost complete systemic availability, slightly longer biological half life and ease of administration, we suggest that the s.c. route be preferred over the i.m. route for amikacin administration in goats. Amikacin at a dose level of 8 mg/kg body weight at 12 h intervals would result in a therapeutic peak plasma concentration (Cpmax) of 32.30 micrograms/mL, which is not expected to produce any oto- or nephropathic effects.

Multiple anthelmintic resistance in Haemonchus contortus on a sheep farm in India.

Multiple resistance to benzimidazoles (fenbendazole, albendazole and mebendazole) in a strain of Haemonchus contortus in sheep was detected on a farm where fenbendazole resistance had already been identified. Following a faecal egg count reduction test, this was confirmed by both critical and controlled anthelmintic tests. Different groups of sheep infected naturally or given an experimental infection with the fenbendazole-resistant strain were treated with the recommended doses of various anthelmintics. Compared to the control group, percentage reductions in faecal egg counts of sheep treated with fenbendazole, albendazole, mebendazole, levamisole and morantel varied between 56% and 81% and worm counts between 71% and 86%. The results indicate the presence of multiple anthelmintic resistance in this strain of H. contortus on this farm. Sheep treated with ivermectin and closantel showed 100% reductions in faecal egg and worm counts, suggesting high efficacy of these drugs against the population of H. contortus on this farm.

Pharmacokinetics of gentamicin following single-dose parenteral administration to goats.

The disposition kinetics of parenterally administered gentamicin (5 mg kg-1) has been studied in Gaddi goats. The serum concentration-time profile was described by bi-exponential and mono-exponential equations following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration with elimination half-life values of 0.96 +/- 0.09, 2.37 +/- 0.47 and 3.56 +/- 0.39 h, respectively. The apparent volume of distribution following i.v. administration (Vdarea: 0.26 +/- 0.041 kg-1) reflected limited extracellular distribution of the drug. The bioavailability was higher following i.m. administration (96.3%) compared to s.c. (76.9%). In view of the significantly longer biological half-life and larger area under the curve values, the s.c. route may be preferred. It is concluded that a suitable and practical dosage recommendation for gentamicin in goats would be 3.35 mg kg-1 body weight given s.c. at 12 h intervals.

Serum disappearance and urinary excretion of sulfamethoxypyridazine in goats.

Pharmacokinetics and urinary excretion of sulfamethoxypyridazine were determined in goats following single intravenous administration (100 mg/kg body weight). The disposition kinetics of sulfamethoxypyridazine could be best described by a 2-compartment open model. The distribution and elimination half life of the drug were 0.10 +/- 0.03 and 6.28 +/- 0.44 h, respectively. The values of apparent volume of distribution at steady state and total body clearance were found to be 0.39 +/- 0.02 l/kg and 0.73 +/- 0.06 ml/kg/min, respectively. The degree of acetylation was low as it ranged between 4.49 +/- 1.96 to 25.07 +/- 6.31% of the total drug in serum with an overall mean of 11.99 +/- 1.66%. Cumulative urinary excretion of sulfamethoxypyridazine was very low as only 2.97 +/- 0.50% of the total administered dose was excreted in urine during 24 h. The dosage regimen in goats would be 37.00 and 27.15 mg/kg body weight as the priming and maintenance doses respectively, to be repeated at 12 h intervals by intravenous route to achieve the bacteriostatic level of > or = 25 micrograms/ml.

Indirect excitatory actions of histamine on isolated chicken oesophagus.

The histamine-induced contraction on chicken oesophagus was antagonised non-competitively by atropine, hexamethonium, cocaine, methysergide, indomethacin, theophylline and verapamil. Physostigmine slightly potentiated the excitatory action of histamine. These results indicate that histamine excreted its excitatory action by involving a number of mechanisms as suggested in guinea pig oesophagus.

An outbreak of haemonchosis associated with anthelmintic resistance in sheep.

An outbreak of haemonchosis associated with anthelmintic resistance was recorded in a flock of 150 crossbred lambs. Closantel and ivermectin were 100% effective against Haemonchus contortus while fenbendazole and morantel reduced faecal egg counts by 87 and 29%, respectively. Levamisole showed an efficacy of 95%. At double the recommended dose (10 mg kg-1), fenbendazole had an efficacy of 99% against H. contortus infection. This appears to be the first report of an outbreak of haemonchosis associated with fenbendazole and morantel resistance in a strain of H. contortus in sheep.

Efficacy of closantel against fenbendazole and levamisole resistant Haemonchus contortus in small ruminants.

Sheep infected with a fenbendazole resistant strain of Haemonchus contortus and goats with a levamisole resistant strain of the same parasite were used to evaluate the anthelmintic efficacy of closantel. Closantel at the rate of 10 mg/kg body weight was 100% effective against the 2 resistant strains of the parasite as indicated by faecal egg count and worm reduction. The efficacy of fenbendazole in sheep and of levamisole in goats was 56.68 and 76.90%, respectively.

Pharmacokinetics and urinary excretion of sulfadiazine in buffalo calves.

Pharmacokinetics and urinary excretion of sulfadiazine were determined in buffalo calves following single oral administration (150 mg/kg). Kinetic evaluation of plasma levels was performed using a 2-compartment model. The absorption half-life and elimination half-life were 3.41 +/- 0.63 and 13.75 +/- 1.94 h, respectively. Based on this study, an optimal dosage regimen of sulfadiazine in buffalo calves would be 165 mg/kg, followed by 75 mg/kg at 12-h intervals. Sulfadiazine was mainly excreted in the urine as free amine, while the percentage of acetylated sulfadiazine was comparatively low.