Disposition Kinetics of Amitraz in Lactating Does

Amitraz, a member of the formamidine pesticide family, commonly used for ectoparasite control, is applied as a dip or low-pressure hand spray to cattle and swine, and the neck collar on dogs. Data on amitraz were generated mainly on laboratory animals, hens, dogs, and baboons. The data on the toxicity and disposition of amitraz in animals and its residues in the milk are inadequate. Therefore, the present study was intended to analyze the disposition kinetics of amitraz and its pattern of elimination in the milk of lactating does after a single dermal application at a concentration of 0.25%. Blood at predetermined time intervals and milk twice daily were collected for eight days post application. The drug concentration was assayed by high-performance liquid chromatography (HPLC). Amitraz was detected in whole blood as early as 0.5 h, which attained a peak concentration at 12 ± 5 h, followed by a steady decline; however, detection persisted until 168 h. Amitraz was present in the blood at its 50% Cmax even after 48 h, and was still detectable after 7 days. The disposition after a single dermal application was best described non-compartmentally. The mean terminal half-life (t1/2), mean residence time (MRT), and area under the curve (AUC0–t) were 111 ± 31 h, 168 ± 39 h, and 539 ± 211 µg/mL/h, respectively. The apparent volume of distribution (Vdarea) was 92 ± 36 mL/g with an observed clearance (Cl) of 0.57 ± 0.33 mL/kg/h. Thus, the drug was well absorbed, widely distributed and slowly eliminated from the animal body. Amitraz achieved milk concentration approximating 0.2 per cent of the total dose after a single exposure and the steady-state elimination of amitraz in milk above the recommended maximum residue limit (MRL) of 0.01 mg/kg can act as a source of public health concern when applied on lactating animals.

Disposition kinetics of ceftriaxone and determination of its therapeutic dose in dogs

Purpose: To evaluate the disposition kinetics of ceftriaxone (CFZ) in dogs with a view to determining its therapeutic dose and dosing frequency.Methods: Twelve (12) Basenji dogs (n = 4), divided into 3 groups (A, B and C), were used for the study. Ceftriaxone was administered intramuscularly at doses of 12.5, 25, and 50 mg/kg once to groups A, B and C respectively. Plasma CFZ concentration was determined by agar well diffusion assay at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h post-treatment, and the pharmacokinetic parameters were determined.Results: Intramuscular injection of CFZ to dogs resulted in rapid absorption, distribution and elimination (p < 0.05). The elimination half-life was short and did not change significantly with increase in dose. Serum concentration of CFZ changed significantly (p < 0.05) with increase in dose of CFZ. The maximum serum concentration (Cmax, 15.00 ± 1.18, 141.37 ± 15.87 and 259 ± 5.21 μg/mL) for groups A, B and C respectively were significantly (p < 0.05) different. The steady state CFZ concentrations; 0.94, 8.81 and 16.19 μg/mL for groups A, B and C, respectively, were significantly (p < 0.05) different. However, there was no significant difference in the time to reach steady state concentrations (Tmax, 00±0.021, 4.00±0.10 and 4.30±0.12 for groups A, B and C respectively). The therapeutic dose of CFZ was therefore determined to be 25 – 50 mg/kg every 4 h.Conclusion: Ceftriaxone undergoes rapid elimination in dogs with a short elimination half-life, thus making it an inconvenient prescription for out-patients in veterinary clinics. Keywords: Ceftriaxone, Pharmacokinetic profile, Dogs, Therapeutic dose, Veterinary clinic

Bio-equivalence study of two oral doxycycline formulations (doxycycline kela 75%® and mebcodox 75%®) in broiler Chickens

The present study was designed to assess the comparative bio-equivalence of Doxycycline Kela 75%® and Mebcodox 75%® in healthy broiler chickens after oral administration of both products in a dose of 20 mg doxycycline base/kg.b.wt. Twenty four broiler chickens were divided into two groups. The first group was designed to study the pharmacokinetics of Doxycycline Kela 75%®, while the 2nd group was designed to study the pharmacokinetics of Mebcodox 75%®. Each broiler chickens in both groups were orally administered with 20 mg doxycycline base/kg.b.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 The disposition kinetics of Doxycycline Kela 75%® and Mebcodox 75%® following oral administration of 20 mg doxycycline base/kg.b.wt. revealed that the maximum blood concentration [Cmax] were 3.35 and 3.28 μg/ml and attained at [tmax] of 0.97 and 0.99 hours, respectively.In conclusion: Mebcodox 75%® is bioequivalent to Doxycycline Kela 75%® since the ratios of Cmax, AUC0-24 and AUC0-∞ (T/R) was 0.97, 0.95 and 0.94 respectively. These are within the bioequivalence acceptance range. Mebcodox 75%® and Doxycycline Kela 75%® are therefore bioequivalent and interchangeable.

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 μg/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.