Pharmacokinetics, milk penetration and PK/PD analysis by Monte Carlo simulation of marbofloxacin, after intravenous and intramuscular administration to lactating goats.

The main objectives of this study were (i) to evaluate the serum pharmacokinetic behaviour and milk penetration of marbofloxacin (MFX; 5 mg/kg), after intravenous (IV) and intramuscular (IM) administration in lactating goats and simulate a multidose regimen on steady-state conditions, (ii) to determine the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of coagulase negative staphylococci (CNS) isolated from caprine mastitis in Córdoba, Argentina and (iii) to make a PK/PD analysis by Monte Carlo simulation from steady-state pharmacokinetic parameters of MFX by IV and IM routes to evaluate the efficacy and risk of the emergence of resistance. The study was carried out with six healthy, female, adult Anglo Nubian lactating goats. Marbofloxacin was administered at 5 mg/kg bw by IV and IM route. Serum and milk concentrations of MFX were determined with HPLC/uv. From 106 regional strains of CNS isolated from caprine mastitis in herds from Córdoba, Argentina, MICs and MPCs were determined. MIC90 and MPC90 were 0.4 and 6.4 µg/ml, respectively. MIC and MPC-based PK/PD analysis by Monte Carlo simulation indicates that IV and IM administration of MFX in lactating goats may not be adequate to recommend it as an empirical therapy against CNS, because the most exigent endpoints were not reached. Moreover, this dose regimen could increase the probability of selecting mutants and resulting in emergence of resistance. Based on the results of Monte Carlo simulation, the optimal dose of MFX to achieve an adequate antimicrobial efficacy should be 10 mg/kg, but it is important take into account that fluoroquinolones are substrates of efflux pumps, and this fact may determine that assumption of linear pharmacokinetics at high doses of MFX may be incorrect.

Allium cepa as a biomonitor of ochratoxin A toxicity and genotoxicity.

Ochratoxin A (OTA) is a toxin produced by Aspergillus and Penicillum moulds. Since OTA has not yet been evaluated in plant systems, this paper focused on describing the controversial effect OTA in an Allium root test model, which has known sensitivity to genotoxins and could be useful in toxin screening. Analyses of root growth and the root meristematic zone in response to OTA treatment were undertaken. The results show OTA toxicity to root growth at a concentration of 10 ug.ml(-1) associated with inhibition of proliferation activity. Cytological changes observed in the Allium chromosome aberrations assay, at a concentration of 5.0 ug.ml(-1), showed that OTA was able to induce genotoxicity at the chromosome level. These results indicate that plants cells (Allium cepa) are very sensitive to the mycotoxin OTA, as observed at the highest concentration. Under these conditions, OTA produced toxicity and cytogenetic injury. Evidence in vitro and in vivo indicates that OTA can induce damage at the DNA level.

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.

Pharmacokinetics of miocamycin following intravenous administration to cattle.

The plasma pharmacokinetics for a single intravenous dose (10 mg/kg body weight) of miocamycin (a 16-membered macrolide drug) was investigated in Holando Argentino cattle (n = 5). Blood drug concentrations were determined by a microbiological method and data were best-fitted to a two-compartment open model. The pharmacokinetic profile consisted of a short distribution phase (t1/2 alpha = 7.41 +/- 0.53 min), followed by an extended terminal elimination phase (t1/2 beta = 2.49 +/- 0.23 h). The volume of distribution at steady-state was large (2.13 +/- 0.17 l/kg), suggesting extensive tissue distribution, the clearance value was 0.60 +/- 0.03 l/h.