The pharmacokinetics of thiamphenicol in lactating cows

The pharmacokinetics of thiamphenicol were studied after intravenous and intramuscular administration of 25 mg/kg body weight in lactating cows. Distribution (t _1/2) and elimination (t _1/2) half-lives of 6.10±1.39 min and 1.60±0.30 h, respectively, were obtained after intravenous administration. The body clearance was 3.9±0.077 ml/kg per min and the apparent volume of distribution was 1220.79±256.67 ml/kg. The rate at which thiamphenicol appeared in the milk, as indicated by the penetration half-life (t _1/2P) (serum to quarters), was found to be 36.89±11.14 min. The equivalent elimination half-life (t _1/2E) (quarters to serum) from the milk was 3.62±1.06 h and the peak thiamphenicol concentration in the milk was 23.09±3.42 µg/ml at 2.5±0.32 h.After intramuscular injection, the elimination half-life was 2.2±0.40 h, the absorption half-life was 4.02±1.72 min and the peak concentration in the serum was 30.90±5.24 µg/ml at 23±8.4 min. The bioavailability after intramuscular administration approached 100%. The penetration half-life was 50.59±6.87 min, the elimination half-life was 5.91±4.97 h and the mean peak concentration in the milk was 17.37±2.20 µg/ml at 3.4±0.22 h.Abbreviations AUC area under the concentration-time curve - CAP chloramphenicol - C _max peak concentration - IM intramuscular - IV intravenous - TAP thiamphenicol - t _1/2 distribution half-life - t _1/2 elimination half-life - V _c volume of central compartment - V _d volume of distribution     

Some Pharmacokinetic Parameters of Oxfendazole in Sheep

Soraci, A.L., Mestorino, N. and Errecalde, J.O., 1997. Some pharmacokinetic parameters of oxfendazole in sheep. Veterinary Research Communications, 21 (4), 283-287     

Pharmacokinetic disposition of triclabendazole in cattle and sheep; discrimination of the order and the rate of the absorption process of its active metabolite triclabendazole sulfoxide

A comparative pharmacokinetic study was conducted to determine the order and the rate of absorption of triclabendazole (TCBZ) in cattle and sheep. A commercial suspension of TCBZ (Biofasiolex, Biogénesis S.A., Argentina) was administered at a dose rate of 10 mg/kg by the oral route to six Holstein female calves and six Corriedale female sheep. The plasma concentration profiles of the metabolites triclabendazole sulfoxide (TCBZ-SO) and triclabendazole sulfone (TCBZ-SO₂) were analysed by means of the non-compartmental method. The order of the absorption process of the active metabolite, TCBZ-SO, was determined by construction of curves of cumulative absorbed fraction of the drug by means of the Wagner-Nelson method. The appearance of TCBZ-SO in plasma of cattle and sheep resembles the entry of a constant quantity of drug into the organism per unit time. This is explained by the reservoir effect of the rumen, which acts as a biological slow-release system for TCBZ-SO and its precursor TCBZ to the posterior digestive tract where they are absorbed. The plasma concentration profiles of TCBZ-SO in both species were well described by a one-compartment open model with zero-order process of absorption and first-order process of elimination. The values of AUC_0-∞ and C _max of TCBZ-SO did not differ between species, while other kinetic parameters except for λ _z had higher values in calves than in sheep. In the case of TCBZ-SO₂, t _max was the only parameter that did not differ between species, while other kinetic parameters except for λ _z had higher values in calves than in sheep.     

The pharmacokinetics of a slow-release theophylline preparation in horses after intravenous and oral administration

The pharmacokinetics of a slow-release theophylline formulation was investigated following intravenous and oral administration at 10 mg/kg in horses. A tricompartmental model was selected to describe the intravenous plasma profile. The elimination half-life (t1/2) was 16.91 ± 0.93 h, the apparent volume of distribution (V _d) was 1.35 ± 0.18 L/kg and the body clearance (Cl_B) was 0.061 ± 0.009 L kg^–1 h. After oral administration the half-life of absorption was 1.24 ± 0.30 h, and the calculated bioavailability was above 100%. Thet1/2 after oral administration was 18.51 ± 1.75 h, only a little longer than that after intravenous administration. The slow release formulation did not exhibit any advantage in prolonging thet1/2 of theophylline in the horse.     

Efficacy of injectable doramectin in the therapy and control of Dermatobia hominis infestations in Latin America

Three studies were conducted in Latin America, one in Brazil, one in Venezuela and one in Argentina, using a common protocol to investigate the efficacy of a single subcutaneous injection of doramectin at 200 μg kg⁻¹ (1 ml per 50 kg) for the treatment and control of Dermatobia hominis infestations in cattle raised under commercial conditions. In each study, two groups of 20 animals each were allocated on the basis of D. hominis nodules present 24 h before treatment to a treated group (T1), or to a control group (T2) which received saline solution at 1 ml per 50 kg of live weight. All cattle were injected in the mid-dorsal cervical region and examined on treatment day and 2, 7, 15 and 30 days post-treatment (p.t.). At each observation day the number of D. hominis nodules was counted and the viability of the larvae inside them was assessed and recorded. Treatment with doramectin was 100% effective in eliminating D. hominis larvae and in controlling the re-establishment of the parasite under field conditions of continuous reinfestation. During the first 48 h p.t., dead larvae of different ages were found outside or partially outside the nodules in animals of the doramectin groups. After 48 h p.t., no live larvae were found inside existing nodules, nor did new nodules develop in animals of the doramectin groups in any of the three studies. When compared with nodule counts in the control group on the same observation day or with parasite burdens on the same animal before treatment, doramectin-treated animals began to eliminate parasitic nodules at 48 h p.t. Efficacy reached 100% at 7 days p.t. and remained at 100% on subsequent observation days (P<0.05). None of the doramectin-treated animals exhibited any clinical signs of adverse reaction to medication.     

Pharmacokinetics of ricobendazole in calves

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.     

Pharmacokinetics of Ricobendazole After its Intravenous,Intraruminal and Subcutaneous Administration in Sheep

Ricobendazole (RBZ) was administered in sheep at the dose rate of 5 mg/kg by intravenous (i.v.) route as a 10% experimental solution, by the intraruminal (i.r.) route as a 10% experimental suspension, and by the subcutaneous (s.c.) route as a 10% commercial formulation available in Argentina. Blood samples were drawn during a 60 h period. Plasma concentrations of RBZ and its inactive metabolite albendazole sulphone (ABZSO₂) were determined by high-performance liquid chromatography. The pharmacokinetic parameters were determined by compartmental analysis. The fitting of the data was done by weighted least-squares non-linear regression analysis. The pharmacokinetic parameters were estimated for every animal by simultaneous fitting of the plasma concentrations profiles of RBZ obtained after its administration by the three routes. The kinetic analysis of ABZSO₂ was performed by a statistical moment approach. Ricobendazole bioavailability was poor after i.r. administration, whereas high and sustained plasma concentrations and higher bioavailability were obtained after s.c. administration. A simple two-compartment open model explains in a mechanical sense the pharmacokinetic behaviour of RBZ in sheep and allows us to estimate the real first-order constant rate of absorption and the loss of drug from the absorption site after its administration by s.c. and i.r. routes.     

The Effects of the Method of Calculation on the Evaluation of the Pharmacokinetic Parameters of Oxytetracycline After Intravenous Administration to Calves

Errecalde, J.O., Mestorino, N. and Mariño, E.L., 1997. The effects of the method of calculation on the evaluation of the pharmacokinetic parameters of oxytetracycline after intravenous administration to calves. Veterinary Research Communications, 21 (4), 273-281The aim of this study was to assess the differences in the values of the pharmacokinetic parameters attributable to the use of either linear or nonlinear regression analysis and to find the effect of weighting schemes on these differences. Six calves received 20 mg/kg oxytetracycline i.v. Blood samples were drawn during 72 h. The assay of the drug was performed microbiologically. A bicompartmental pharmacokinetic model was used, kinetic analysis being carried out by linear regression (LR) and by weighted least-squares nonlinear regression (WLSNLR). Statistical analysis included a test for normality, the Kruskall-Wallis test and ANOVA with log transformation.The A0, and B0 did not show any statistically significant differences attributable to the mathematical method used. On the other hand, the statistically significant differences in the values found using the Kruskall-Wallis test and ANOVA with log transformation could be attributed to the different methods employed. ANOVA with log transformation determined statistically significant differences between the parameters obtained by linear analysis and those obtained by WLSNLR when the weighting (w) was 1. When weights were 1/x, 1/x2 or 1/ x, no statistically significant differences were found. The optimal weighting scheme was w = 1/x2 because of a more homogeneous scatter and random distribution of residuals about the abcissa axis in a plot of weighted residuals in the ordinate versus time in the abcissa. It was concluded that the use of these different procedures can give major variations in the apparent value of , the most important pharmacokinetic parameter. The correct selection of the weighting procedure is therefore fundamental in obtaining the best estimate of this pharmacokinetic parameter in WLSNLR.     

A discriminatory study of a pharmacokinetic model for intramuscular gentamicin in sheep

The resulting serum concentrations were measured in six ewes after intramuscular administration of 10 mg/kg of gentamicin. The model providing the best fit for the experimental data was determined both by linear regression analysis between the experimental and theoretical values and by means of the Minimum Akaike Information Criterion Estimation (MAICE) test.Linear regression analysis showed certain differences favouring the monocompartmental model although the advantage was not conclusive. The MAICE test, however, permitted a clear discrimination in favour of the same model. When linear regression analysis is not conclusive, the MAICE test represents a good alternative.