Population Pharmacokinetics of Tobramycin in Horses

Population pharmacokinetics of tobramycin was investigated in 28 healthy horses, with an aim to assess interindividual variability in the disposition of the antibiotic. Additionally, a covariate model for improved prediction of the concentrations in a particular animal was developed. A two-compartmental model best described the data. The final population covariate regression model was based on relationships between body weight and central and peripheral volumes of distribution, and between creatinine clearance and systemic tobramycin clearance. The value of population systemic tobramycin clearance and its interindividual variation (CV) were 0.087 L.hr⁻¹.kg⁻¹ and 6.0%, respectively. The respective values for central and peripheral volumes of distribution were 0.652 L.kg⁻¹ with CV of 17.7% and 1.56 L.kg⁻¹ with CV of 4.5%. In horses with decreased glomerular filtration rate, lower tobramycin clearance is predicted with the population model that requires administration of lower dose than that accepted for treatment of horses with normal kidney function. Population pharmacokinetic analysis allows study of basic disposition of tobramycin in horses with sparse data. The prediction power of the regression model was improved by inclusion of covariables such as body weight and creatinine clearance. This model can be used in direct patient care for the construction of dosing strategy in individual clinical cases.     

Interactions between the introduced fungal pathogen Entomophaga maimaiga and indigenous tachinid parasitoids of gypsy moth Lymantria dispar in Bulgaria

Interactions between the gypsy moth, Lymantria dispar L. (Lepidoptera: Erebidae), pathogenic fungus Entomophaga maimaiga, and the tachinid parasitoid (Diptera: Tachinidae) complex in gypsy moth larvae were investigated in Bulgaria, where E. maimaiga was recently released as a biological control agent. Gypsy moth larvae were collected in oak stands where E. maimaiga was originally introduced (nine sites) and in sites where the pathogen has invaded by natural extension of the range (ten sites). In total, 4,375 host larvae were examined and 401 tachinid larvae emerged from parasitized hosts. Host mortality caused by tachinids varied from 0 to 48.5% among sites, with an overall average of 9.2%. Emerging adult tachinid parasitoids included 54 individuals belonging to six species: Compsilura concinnata, Exorista larvarum, Senometopia separata, Senometopia excisa, Drino incospiqua and Zenilia libatrix; the remaining parasitoids (86.5%) died in the pupal stage. E. maimaiga azygospores were observed on puparia surfaces, an indication that the gypsy moth host larvae were infected with the fungus. No azygospores were observed in parasitoid tissues. The high parasitoid mortality may be the result of the competition with E. maimaiga during development in the same host.     

Pharmacokinetic studies on tobramycin in horses

The objective of the study was to evaluate the pharmacokinetics of tobramycin in plasma and urine in the horse (n = 7) after intravenous administration of a dose of 4 mg/kg b.w. Plasma tobramycin concentrations were assayed microbiologically and by means of HPLC analyses. Pharmacokinetic parameters, calculated on the basis of concentrations determined with the microbiological assay were not statistically different from those obtained when data from HPLC analysis were used, but the microbiological assay was more sensitive in the detection of low plasma and urine values. The values of the total body clearance (Cl(B)) were 101.4 +/- 30.1 and 130.0 +/- 49.9 mL/kg/h, respectively. The overall extraction ratio was 2.9%. The determined capacity of elimination of tobramycin in horses was similar to those for other aminoglycosides. Within 24 h after treatment, 57.6 +/- 12.2% of injected antibiotic was excreted in the urine.