The pharmacokinetics of ricobendazole (RBZ) and its major metabolite albendazole sulphone (ABZSO2) were studied in six calves, after administration of RBZ (7.5 mg/kg), using a 10% experimental solution by the intravenous (i.v.) route, a 10% commercial solution by the subcutaneous (s.c.) route, and a 10% experimental suspension by the intraruminal (i.r.) route. Blood samples were drawn during a 60-h period. Plasma drug and metabolite concentrations were determined by HPLC. The pharmacokinetic evaluation in each case was prepared by weighted least-squares nonlinear regression analysis. Ricobendazole i.v. data were best fitted by a two-compartment model. The best pharmacokinetic exponents and coefficients were estimated, and the pharmacokinetic variables for RBZ and ABZSO2 were calculated from them. Similar patterns of plasma disposition were found for RBZ after i.r. and s.c. administration, suggesting delayed release from the s.c. site resembling the slow release of the drug from the rumen.

The pharmacokinetics and bioavailability of cefoperazone (CPZ) were studied following intravenous (IV) and intramuscular (IM) administration of single doses (30 mg/kg) to horses. Concentrations in serum, urine and synovial fluid samples were measured following IV administration. CPZ concentrations in serum, synovial fluid and spongy bone samples were measured following IM administration. After IV administration a rapid distribution phase (t1/2 (alpha): 4.22 +/- 2.73 min) was followed by a slower elimination phase (t1/2(beta) 0.77 +/- 0.19 h). The apparent volume of distribution was 0.68 +/- 0.10 L/kg. Mean synovial fluid peak concentration was 5.76 +/- 0.74 microgram/mliter. After IM administration a bioavailability of 42.00 +/- 5.33% was obtained. Half-life of absorption was 2.51 +/- 0.72 min and t1/2(beta) was 1.52 +/- 0.15 h. The mean synovial fluid and spongy bone peak concentrations at 2 h after IM administration were 2.91 +/- 0.85 microgram/mliter and 5.56 +/- 0.70 microgram/mliter, respectively.

No abstract

Azithromycin is a time-dependent antimicrobial with long persistence. The main characteristics of azithromycin suggest that it could be useful for treating bovine mastitis caused by Staphylococcus aureus. To investigate this possibility, its pharmacokinetic (PK) behavior was studied. Six Holstein lactating cows with subclinical mastitis were administered two 10 mg/kg intramuscular (i.m.) doses of azithromycin, with a 48-h interval. Milk and plasma concentrations were measured by microbiological assay. The MIC(90) was determined in 51 S. aureus isolations to calculate pharmacokinetic/pharmacodynamic (PK/PD) parameters. Milk maximal concentration (C(max)) was 7.76 +/- 1.76 microg/mL (16.67 h post-first administration) and 7.82 +/- 2.18 microg/mL (14 h post-2(nd) administration). In plasma C(max) was 0.18 +/- 0.03 microg/mL (2 h post-1(rst) administration) and 0.11 +/- 0.03 microg/mL (14 h post-2(nd) administration). Azithromycin was eliminated from the milk with a half-life (T(1/2)lambda) of 158.26 +/- 137.7 h after 2(nd) administration, meanwhile plasma T(1/2)lambda resulted shorter(13.97 +/- 11.1 h). The mean area under the concentration vs. time curve from 0 to 24 h (AUC(0-24h)) was 153.82 +/- 34.66 microg.h/mL in milk secretion and 2.61 +/- 0.59 microgxh/mL in plasma. Infection presence in the quarters had a significant effect (P < 0.05) on the area under the concentration vs. time curve from 0 to infinity (AUC(0-infinity)) and clearance from the mammary gland (Cl(mam)/F). Moreover, it had influence on milk bioavailability (F(milk)), T(1/2)lambda, AUC(0-infinity) and mean residence time (MRT) in milk, which values resulted increased in mastitic quarters. In this study, it was determined that the production level and the mammary health status have an influence on PK parameters of azithromycin treatments in bovine mastitis.

It is well established that the efficacy of any anthelmintic drug depends not only on its affinity for specific parasite target sites but also on its ability to reach high and sustained drug concentrations where the parasites are located.Ivermectin is one of the most useful anti-parasitic agents. It belongs to the family of avermectins that are highly lipophilic macrocyclic lactones. It is a fermentation product of Streptomyces avermitilis. One of the most important characteristics of ivermectin is its wide spectrum of activity involving endo-and ectoparasites.Ivermectin is effective when it is applied orally, parenterally or topically. Its absorption is rapid by any of these routes of administration (Campbell, 1989(Campbell, , 1993.Mange is an ectoparasitic disease produced by the mite Psoroptes ovis. It has major economic importance in South America, especially Argentina, Chile and Uruguay. It is anticipated that in the diseased animal there are kinetic modifications largely dependent on the change of body condition. The objective of the present paper was to determine the pharmacokinetic changes of ivermectin when applied subcutaneously to healthy animals and animals carrying natural mange infections.Six adult and healthy sheep (weighing 50 ± 6 kg) and five sheep naturally infested with psoroptic mites and showing mange lesions on at least 30% of their body surface (weighing 43 ± 6 kg) received 200 lg/kg ivermectin subcutaneously, the sampling times being at the following post-administration days: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 20, 25 and 30. Plasma was separated by centrifugation and kept frozen at )20°C until assayed. Assay was performed by high-performance liquid chromatography (HPLC). The recovery was 85% and the quantitation limit was 0.1 ng/mL. Variability was lower than 8%. The HPLC system was a Shimadzu LC-10 AS pump and TM III 1311 model fluoromonitor. The column was a C8 reverse phase lichrospher and the mobile phase was glacial acetic acid/ methanol/acetonitrile (9:200:291 mL) at a flow rate of 1.5 mL/ min. Reagents were HPLC grade. Extraction was accomplished by the solid-liquid method with C18 cartridges. The eluate was evaporated, derivatizated and injected into the HPLC system (Alvinerie et al., 1987). Pharmacokinetic analysis was performed by a linear regression program known as Estrip (Brown & Manno, 1978). Pharmacokinetic parameters were obtained following Baggot (1977) and Gibaldi and Perrier (1975). Statistically significant differences were considered with a probability <0.05 by using Student's t-test after log transformation of the data. Figure 1 shows the mean plasma concentration-time curve of ivermectin in healthy and infested sheep. In Table 1, a comparison between the mean pharmacokinetic parameters of ivermectin in healthy and diseased sheep is shown. A onecompartment open model with first-order absorption was used to describe plasma kinetics. Maximum plasma concentration (C max ) was collected earlier in sheep infected with mange (T max 0.90 days) than in healthy sheep (T ma...

The serum and synovial pharmacokinetics of amoxycillin (AMX) were studied after i.v. administration at a dosage of 40 mg/kg to normal horses and horses with induced aseptic carpal arthritis. The best estimates of serum and synovial pharmacokinetic parameters were calculated by mono or bivariable non-linear regression analysis. A biexponential equation was used to describe the concentration vs. time profiles in both normal and arthritic horses. There were no serum kinetic differences between normal and arthritic horses. There were, however, major synovial kinetic changes between these groups. The rate of penetration from serum to synovial fluid was larger in arthritic animals, indicating better penetration in this case. On the other hand, the rate of disappearance from synovial fluid was larger in normal horses, indicating more persistence of the drug in the diseased joint. Synovial AMX availability increased from 21% in normal horses to 79% in arthritic horses. These findings support the use of AMX for the treatment of infectious synovial joint disease produced by susceptible organisms in horses.

The pharmacokinetics and bioavailability of theophylline in horses were investigated following both intravenous and intragastric administration of aminophylline solutions at doses corresponding to 15 and 10 mg/kg theophylline base. A rapid distributive phase with a half-life of approximately 15-30 min was followed by a slower elimination half-life averaging 15-17 h. The apparent volume of distribution averaged 850-900 ml/kg. Theophylline, administered as aminophylline solution, was both rapidly and completely absorbed from the equine digestive tract. Based on the bioavailability and disposition kinetics of theophylline, an intragastric dosage regimen for aminophylline consisting of the administration of 5 mg/kg at 12 h intervals would be expected to maintain plasma theophylline concentrations within the therapeutic range.

No abstract