Pharmacokinetics and pharmacodynamics of chlorpyrifos in male and female cattle after topical administration

The aim of this work was to study the pharmacokinetic behaviour and the inhibitory effect on acetylcholinesterase and butyrylcholinesterase activities of chlorpyrifos in male and female cattle after pour-on administration. Determination of cholinesterase activity in plasma and erythrocyte was carried out according to Ellman kinetic method. The mean baseline activities were 9338.39 ± 1331.61 and 13220.69 ± 2274.18 to acetylcholinesterase and 624.65 ± 39.32 and 641.68 ± 88.08 IU/L to butyrylcholinesterase in females and males, respectively. Acetylcholinesterase was the predominant form of cholinesterase analyzed, with low levels of butyrylcholinesterase. The basal acetylcholinesterase activities of the bulls were significantly greater than those of cows. The inhibitory effect of topical chlorpyrifos administration was lower on butyrylcholinesterase than on acetylcholinesterase. Chlorpyrifos peak plasma concentration (male:10.920 ± 4.18; female:12.12 ± 3.88 μg/L) were reached at 11.92 ± 9.19 and 8.17 ± 7.67 h in male and female, respectively. The values of area under curve were 185.96 ± 168.45 and 278.89 ± 270.00 μg·h/L and mean residence time were 13.95 ± 8.10 and 14.90 ± 9.80 h in male and female, respectively.     

Surfactant and water migration in unsaturated sand

• 1 In unsaturated coarse disperse materials such as sand, the water on the surface is continous and ‘deep’ enough to be an adequate medium for the migration of surface active substances (SAS).
• 2 The influence of the tangential force on water migration in unsaturated coarse disperse material is studied by compensating the capillary pressure difference caused by the surface tension gradient.
• 3 The influence on water migration in unsaturated disperse materials exerted by the additional pressure difference, originating from SAS migration, is comparable to that exerted by capillary pressure difference.

     

Surfactants and soil water evaporation and migration

1. Water evaporation from soil and sand columns is smaller when the surfactant is placed on the surface, and larger when it is located at the bottom. Water evaporation from soil and sand mixed with the surfactant is as high as without the surfactant. 2. The fact that water evaporation from soil and sand depends on the location of the surfactant in the column is accounted for by the dominant role of migration but not by the suppressive action of the surfactant film on water evaporation. 3. Water migration from sites with surfactant towards sites without surfactant is caused by two pressures: the capillary and the additional pressure arising from the spreading of the surfactant. 4. The importance of the additional pressure on water migration is shown by experiments which rule out the existence of a capillary pressure difference.     

Evidence that active transmission of porcine cysticercosis occurs in Venezuela

There is a paucity of quantitative data on the status of porcine cysticercosis in Venezuela, information which is essential for understanding the level of disease transmission. This study was, therefore, conducted in a typical small rural community in Yaracuy State, Venezuela, where previous cases of human Taenia solium taeniasis/cysticercosis had been reported and where the free-ranging pig management practices and the lack of rudimentary sanitary facilities indicated an obvious risk for transmission of the disease. Serum samples from 52 village pigs were screened by enzyme-linked immunosorbent assays for anti-cysticercal antibodies (Ab-ELISA), using T. solium cyst fluid as the antigen and the HP10, monoclonal antibody-based, antigen trapping ELISA for parasite antigen (HP10 Ag-ELISA). Significantly, a high proportion of the animals (65.4% for the Ab-ELISA and 42.3% for the HP10 Ag-ELISA) were sero-positive. Five of the pigs, which were selected on that basis of positive tongue palpation, were killed for autopsy, and large numbers of viable cysticerci were found in the carcases. This unequivocal documentation of porcine cysticercosis in Venezuelan pigs presents clear evidence that T. solium is actively transmitted in Venezuela. Further detailed studies and implementation of appropriate control measures are therefore indicated.     

Microbiological screening test validation for detection of tylosin excretion in milk of cows with low and high somatic cell counts

Antibiotic residues in milk above tolerance levels interfere with dairy product processing and pose potential health risks to consumers. Residue avoidance programmes include, among other components, the observance of withdrawal times indicated in label instructions. Persistence of antibiotics in milk following treatment is influenced by drug, dosage, route of administration, body weight and mammary gland health status. Compositional changes that take place during intramammary infection (IMI) can affect antibiotic excretion in milk, thus modifying milk withdrawal time. The objectives of this study were to validate sensitivity and specificity of a qualitative microbiological method (Charm AIM-96) to detect tylosin in bovine composite milk and to determine the influence of subclinical IMI in tylosin excretion following intramuscular administration. For test validation, two groups of approximately 120 cows were used; one received a single intramuscular injection of tylosin tartrate at a dose of 20 mg/kg, while the other group remained as untreated control. Test sensitivity and specificity were 100% and 94.1% respectively. To determine the influence of subclinical IMI in tylosin excretion, two groups of seven cows, one with somatic cell counts (SCC) < or =250 000 cells/ml and the other with SCC > or =900 000, were administered a single intramuscular injection of tylosin tartrate at a dose of 20 mg/kg. Milk samples were obtained every 12 h for 10 days following treatment. Milk tylosin excretion averaged between 5 and 9 days for cows with low and high SCC respectively (P < 0.0001). Compositional changes in cows with high SCC most likely affect the pharmacokinetic characteristics of tylosin, extending the presence of the antibiotic in milk, thus influencing milk withdrawal times.     

Some Comparative Aspects of the Pharmacokinetics of Tylosin in Buffaloes and Cattle

The pharmacokinetics of tylosin were compared in cattle (Bos taurus) and buffaloes (Bubalus bubalis). Six animals received each a single dose of 10 mg/kg of tylosin tartrate by the intramuscular route. The serum concentration (C _max) and the volume of distribution (V _d) presented significant differences between the two species. C _max was 0.40 ± 0.046 µg/ml for buffaloes and 0.64 ± 0.068 µg/ml for cattle. V _d was 1.91 ± 0.12 L/kg and 1.33 ± 0.09 L/kg for buffaloes and cattle, respectively. However, as the present study did not show considerable differences in the pharmacokinetics of tylosin in buffaloes and cattle, similar dosage regimes of this drug can be recommended for both species.     

Chronobiological variations of indomethacin pharmacokinetic parameters in sheep

A two-phase study to investigate the influence of administration time on pharmacokinetics of indomethacin in sheep was performed. In phase I, 12 animals were allocated to four groups, each corresponding to a different time: 08:00, 14:00, 20:00, 02:00 h. Sheep received an intravenous administration of 1 mg/kg indomethacin. In phase II, each group was administered indomethacin with a 12-h difference compared to Phase I. The trial was performed in autumn, and animals were subjected to a natural light:dark cycle of 10:14 h. Blood samples were taken and processed by high performance liquid chromatography (HPLC) with ultraviolet detection. For each pharmacokinetic parameter, an analysis of variance was performed to outline the existence of chronobiological variations. Concentration at zero time (C0), hybrid constant for distribution and its half life, hybrid constant for elimination and its half-life, volume of distribution (V(d)), area under the curve (AUC(infinity)) and clearance rate (Cl), presented chronobiological variations (P < 0.05) and were fitted to a cosine equation. The following parameters adjusted to circadian rhythms: C(0) (acrophase: 13.9788 h); AUC(infinity) (acrophase: 13.4377 h); V(d) (acrophase: 0.8245 h) and Cl (acrophase: 1.4965 h). It was concluded that pharmacokinetic parameters of intravenously injected indomethacin in sheep would behave in a different, though predictable, manner according to the animal's biological clock.     

Pharmacokinetics of indomethacin in sheep after intravenous and intramuscular administration

The pharmacokinetics of indomethacin (1mg/kg) was determined in six adult sheep after intravenous (i.v.) and intramuscular (i.m.) injection. Plasma concentrations were maintained within the therapeutic range (0.3–3.0 μg/mL) from 5 to 50 min after i.v. and from 5 to 60–90 min after i.m. administration. After two trials, indomethacin best fitted an open two-compartment model. The mean (±SD) volumes of distribution at steady state ( V d_ss) were 4.10 ± 1.40 and 4.21 ± 1.93 L/kg and the mean clearance values ( C l_B) were 0.17 ± 0.06 and 0.22 ± 0.12 L/h.kg for i.v. and i.m. routes, respectively. The elimination phase half-lives did not show any significant difference between routes of injection ( t _½β = 17.4 ± 4.6 and 21.25 ± 4.44 h, i.v. and i.m. respectively). After i.m. administration, plasma maximum concentration ( C _max =  1.10 ± 0.68 μg/mL) was reached 10 min after dosing; the absorption phase was fast ( K _ab = 26 ± 18 h-1) and short ( t _½ab = 2.33 ± 1.51 min) and the mean bioavailability was 91.0 ± 32.8%, although there was considerable interanimal variation. In some individuals, bioavailability was higher than 100%. This fact combined with the slower elimination phase after i.m. than after i.v. administration, could be related with enterohepatic recycling.     

Glutamine and glutamate levels and related metabolizing enzymes in tomato fruits with different shelf-life

Free amino acids composition and glutamate dehydrogenase (GDH) and glutamine synthetase (GS) levels were evaluated in fruits of Lycopersicon esculentum var. esculentum genotypes having standard (cv. Caimanta) and altered (nor and rin mutants) ripening characteristics. Two accessions of the wild L. esculentum var. cerasiforme (LA1385 and LA1673) were also assayed. Shelf-life (SL) of these fruits ranged from 12 (cv. Caimanta) to 36 (nor mutant) days. The relative glutamate content (as percentage of total free amino acid content) of ripe mature fruits differed considerably among lines, having cv. Caimanta and the nor mutant the highest and the lowest values, respectively. A negative correlation between the relative glutamate content and fruit SL was also found. In the standard ripening cv. Caimanta, GS was principally present in green mature fruits while GDH was found in ripe mature fruits. In the other lines, GS and GDH were detected at both maturation stages. Summarizing, standard SL correlates with higher relative glutamate content and reciprocal induction pattern of GS and GDH, while long SL is associated with lower relative glutamate content and simultaneous presence of both enzymes in the pericarp of tomato fruits. These data suggest that the regulation of the level of glutamate, GS and GDH during fruit ripening is related to the final SL of fruits.     

Effects of age on the pharmacokinetics of single dose sulfamethazine after intravenous administration in cattle

Sulphonamides are still being used widely, influenced by the low cost and the efficacy against many common bacterial infections, since they present a broad spectrum of activity. The aim of this study was to determine the effect of age on the pharmacokinetic/pharmacodynamics (PK/PD) integration of intravenous sulfamethazine (60 mg/kgbw) in cattle, and the possible therapeutic outcomes. Six healthy female calves, at the age of one, three, seven and fifteen weeks were used. Normality analysis was assessed with the Shapiro-Wilk test. Non-parametric tests for paired data were used. Plasma concentrations were quantified using HPLC/uv. Differences were found between one-three-weeks-old calves and seven-fifteen-weeks-old calves, in pharmacokinetic parameters (clearance, area under the concentration-time curve and elimination half-life) and in the PK/PD integration. The ratios obtained in PK/PD integration (T>MIC, WAUC) confirm that it is necessary to apply twice the dose of sulfamethazine in ≥ 7 weeks-old cattle to reach a satisfactory dosage regimen (MIC ≥ 32 μg/mL).