Bio-equivalence study of two tilmicosin phosphate formulations (Micotil 300� and Cozina 300�) in broiler chickens

Background: The present study was designed to assess the comparative bio-equivalence of Micotil 300� and Cozina 300� in healthy broiler chickens after oral administration of both products in a dose of 15 mg tilmicosin base/kg body wt.Methods: Twenty four broiler chickens were divided equally into two groups (12 chickens for each group). The first group was designed to study the pharmacokinetics of Micotil 300�, while the 2nd group was designed to study the pharmacokinetics of Cozina 300�. Each broiler chicken in both groups was orally administered with 15 mg tilmicosin/kg body wt. Blood samples were obtained from the wing vein and collected immediately before and at 0.08, 0.16, 0.25, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours after a single oral administration.Results: The disposition kinetics of Micotil 300� and Cozina 300� following oral administration of 15 mg tilmicosin/kg body wt revealed that the maximum blood concentration [Cmax] were 1.73 and 1.67 ?g/ml and attained at [tmax] of 2.01 and 2.04 hours, respectively.Conclusions: Cozina 300� is bioequivalent to Micotil 300� since the ratios of Cmax, AUC0-24 andAUC0-? (T/R) were 0.96, 0.93 and 0.91 respectively. These are within the bio-equivalence acceptance range. Micotil 300� and Cozina 300� are therefore bioequivalent and interchangeable.

Disposition kinetics, in vitro plasma protein binding and tissue residues of tilmicosin in healthy and experimentally (CRD) infected broiler chickens

Background: Several studies assayed the pharmacokinetics of tilmicosin in broilers at a dosage of (25mg/kg.b.wt.). The aim of this study was to investigate the pharmacokinetics and tissue residues of tilmicosin following single and repeated oral administrations (25mg/kg.b.wt.) once daily for 5 consecutive days in healthy and experimentally Mycoplasma gallisepticum and E. coli infected broilers.Methods: After oral administrations of tilmicosin (25 mg/kg.b.wt.) one ml blood was collected from the right wing vein and tissues samples for determination of tilmicosin concentrations and the disposition kinetics of it by the microbiological assay method using Bacillus subtilis (ATCC 6633) as a test organism.Results: In this study, the plasma concentration time graph was characteristic of a two-compartments open model. Following a single oral administration, tilmicosin was rapidly absorbed in both healthy and experimentally infected broilers with an absorption half-life of (t0.5(ab)) 0.45 and 0.52h, maximum serum concentration (Cmax) was 1.06 and 0.69?g/ml at (tmax) about 2.56 and 2.81h, (t0.5(el)) was 21.86 and 22.91h and (MRT) was 32.15 and 33.71h, respectively; indicating the slow elimination of tilmicosin in chickens. The in-vitro protein binding was 9.72±0.83%. Serum concentrations of tilmicosin following repeated oral administration once daily for five consecutive days, almost peaked 2h after each dose with lower significant values recorded in experimentally infected broiler chickens than in healthy ones.Conclusions: This study showed that tilmicosin was cleared rapidly from tissues. The highest residue values were recorded in the lung followed by liver and kidneys while the lowest values were recorded in spleen, fat and thigh muscles. Five days for withdrawal period of tilmicosin suggested in broilers.

Pharmacokinetics of tilmicosin in healthy pigs and in pigs experimentally infected with Haemophilus parasuis

A comparative in vivo pharmacokinetic (PK) study of tilmicosin (TIL) was conducted in 6 crossbred healthy pigs and 6 crossbred pigs infected with Haemophilus (H.) parasuis following oral administration of a single 40 mg/kg dose. The infected model was established by intranasal inoculation and confirmed by clinical signs, blood biochemistry, and microscopic examinations. Plasma TIL concentrations were determined by a validated high-performance liquid chromatography method with ultraviolet detection at 285 nm. PK parameters were calculated by using WinNonlin software. After TIL administration, the main PK parameters of TIL in healthy and H. parasuis-infected pigs were as follows: Area under the concentration-time curve, maximal drug concentration, half-life of the absorption phase, half-life of the distribution phase, and half-life of the elimination phase were 34.86 ± 9.69 vs. 28.73 ± 6.18 µg · h/mL, 1.77 ± 0.33 vs. 1.67 ± 0.28 µg/mL, 2.27 ± 0.45 vs. 2.24 ± 0.44 h, 5.35 ± 1.40 vs. 4.61 ± 0.35 h, and 43.53 ± 8.17 vs. 42.05 ± 9.36 h, respectively. These results of this exploratory study suggest that there were no significant differences between the PK profiles of TIL in the healthy and H. parasuis-infected pigs.

Preparation of Tilmicosin Imprinted Polymers and Its Application to Solid Phase Extraction / 分析化学

Molecularly imprinted polymers (MIPs) with high selectivity to tilmicosin (TIM) were prepared using tylosin(TYL) as dummy template, methacrylic acid(MAA) as monomer, ethylene glycol dimethacrylate (EGDMA) as cross-linker.The effects of 4 porogens including dimethyl formamide, methanol, acetone, and chloroform on the recognition capability of MIPs were investigated.Orthogonal test was used to optimize the preparation of MIPs, and the optimal composition was as follows; 1.0 mmol TYL, 8.0 mmol MAA, 20.0 mmol EGDMA, 6.0 mL chloroform, 20.0 mg azobisisobutyronitrile.The solid phase extraction condi tions and characteristics of MIPs as adsorptive material for the selective extraction and enrichment of TIM were also studied.The recovery of TIM was above 90% when the following procedure was applied to MIPs cartridge: conditioning with methanol and water(pH 9.0), loading with acetonitrile, cleaning with methanol and chloroform respectively, and eluting with 3 mL methanol-ammonia(95:5, V/V).The recovery of TIM on non-imprinted polymers cartridge was only 32%.

Postantibiotic effects and postantibiotic sub-MIC effects of tilmicosin, erythromycin and tiamulin on erythromycin-resistant Streptococcus suis

The postantibiotic effects (PAEs) and postantibiotic sub-MIC effects (PA SMEs) of tilmicosin, erythromycin and tiamulin on erythromycin-susceptible and erythromycin-resistant strains of Streptococcus suis (M phenotype) were investigated in vitro. Tilmicosin and tiamulin induced significantly longer PAE and PA SME against both erythromycin-susceptible and erythromycin-resistant strains than did erythromycin. The durations of PAE and PA SMEs were proportional to the concentrations of drugs used for exposure. The PA SMEs were substantially longer than PAEs on S. suis (P<0.05) regardless of the antimicrobial used for exposure. The results indicated that the PAE and PA SME could help in the design of efficient control strategies for infection especially caused by erythromycin-resistant S. suis and that they may provide additional valuable information for the rational drug use in clinical practice.

In vitro susceptibilities of Leptospira spp. and Borrelia burgdorferi isolates to amoxicillin, tilmicosin, and enrofloxacin

Antimicrobial susceptibility testing was conducted with 6 different spirochetal strains (4 strains of Leptospira spp. and 2 strains of Borrelia burgdorferi) against 3 antimicrobial agents, commonly used in equine and bovine practice. The ranges of MIC and MBC of amoxicillin against Leptospira spp. were 0.05 - 6.25 microgram/ml and 6.25 - 25.0 microgram/ml, respectively. And the ranges of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of amoxicillin against B. burgdorferi were 0.05 - 0.39 microgram/ml and 0.20 - 0.78 microgram/ml, respectively. The ranges of MIC and MBC of enrofloxacin against Leptospira spp. were 0.05 - 0.39 microgram/ml and 0.05 - 0.39 microgram/ml, respectively. Two strains of B. burgdorferi were resistant to enrofloxacin at the highest concentration tested for MBC (> or = 100 microgram/ml). Therefore, the potential role of tilmicosin in the treatment of leptospirosis and borreliosis should be further evaluated in animal models to understand whether the in vivo studies will confirm in vitro results. All spirochetal isolates were inhibited (MIC) and were killed (MBC) by tilmicosin at concentrations below the limit of testing (< or = 0.01 microgram/ml).