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

Author(s):  
Taha Attia ◽  
Amera Abd El Latif ◽  
Saber El-Hanbally ◽  
Hanem El-Gendy

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 0.69μg/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.

Author(s):  
Ashraf Elkomy ◽  
Mohamed Aboubakr

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.


2020 ◽  
Vol 8 (1) ◽  
pp. 54
Author(s):  
Ashraf El-Komy ◽  
Mohamed Aboubakr

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.   


2016 ◽  
Vol 4 (2) ◽  
pp. 144
Author(s):  
Ashraf El-Komy ◽  
Taha Attia ◽  
Amera Abd El Latif ◽  
Hanem Fathy

The pharmacokinetics of marbofloxacin was studied following a single intravenous, oral administration in normal broiler chickens and repeated oral administrations in normal and experimentally E.coli infected broiler chickens. The pharmacokinetic parameters following a single intravenous injection of 2 mg/kg b.wt., revealed that marbofloxacin obeyed a two compartments open model, distribution half-life (t0.5(α)) was 0.25±0.02 h, volume of distribution (Vdss) was 0.76±0.08 L/kg, elimination half-life (t0.5(β)) was 5.43±0.87 h and total body clearance (CLtot) was 0.09±0.002 l/kg/h. Following a single oral administration, marbofloxacin was rapidly and efficiently absorbed through gastrointestinal tract of chickens as the absorption half-life (t0.5 (ab): 0.62±0.02 h). Maximum serum concentration (Cmax) was 1.15±0.01 μg/ml, reached its maximum time (tmax) at 2.53±0.04 h, elimination half-life (t0.5 (el)) was 7.36±0.20 h indicating the tendency of chickens to eliminate marbofloxacin in slow rate. Oral bioavailability was 73.57± 1.90 % indicating good absorption of marbofloxacin after oral administration. Serum concentrations of marbofloxacin following repeated oral administration of 2 mg/kg b.wt. once daily for five consecutive days, peaked 2 hours after each oral dose with lower significant values recorded in experimentally infected broiler chickens than in normal ones. Tissues residues of marbofloxacin in slaughtered normal chickens was highly in those tissues lung, liver, and kidneys in chickens and the chicken must not be slaughtered before 3 days of stopping of drug administration. It was concluded that the in- vitro protein binding was 12.33±0.82%.


2016 ◽  
Vol 4 (2) ◽  
pp. 150
Author(s):  
Mohamed El-Hewaity

The disposition kinetic of tilmicosin (25mg/kg) was studied following oral administration alone, pretreated with amprolium (240 ppm), pretreated with diclazuril (2.5 ppm) and pretreated with toltrazuril (25 ppm) in broiler chickens. The serum tilmicosin concentrations were determined by microbiological assay technique using Bacillus subtilis (ATCC 6633) as the test organism. Following oral administration of tilmicosin, the disposition curve was best described by two-compartment open model. The maximum serum concentration (Cmax) was 1.90 ± 0.11, 1.27 ± 0.13, 1.50 ± 0.14 and 1.41 ± 0.11µg/ml for tilmicosin alone and in the presence of amprolium, diclazuril and toltrazuril, respectively. The elimination half-life (T0.5 (el)) was significantly decreased (5.28 ± 0.30, 5.88 ± 0.33, 6.03 ± 0.25 h, respectively) in amprolium, diclazuril and toltrazuril pretreated broiler chicken compared to tilmicosin alone (7.30 ± 0.41 h). The outcomes illustrated a significant decrease in the interval between doses in amprolium, diclazuril and toltrazuril pretreated broiler chicken compared to tilmicosin alone. Amprolium diclazuril and toltrazuril, resulted in a significance decrease in AUC (12.02 ± 1.14, 15.50 ± 1.26 and 14.56 ± 1.46 µg.h.ml-1, respectively) compared to tilmicosin alone (21.98±1.83 µg.h.ml-1). It is concluded that the administration of amprolium, diclazuril and toltrazuril before tilmicosin would altered its pharmacokinetic profile in broiler chicken.


Author(s):  
Mohamed Aboubakr ◽  
Mohamed Elbadawy

Background: The present study was designed to assess the comparative bioequivalence of Biocillin® and Atcomox87%® in healthy broiler chickens after oral administration of both products in a dose of 20 mg amoxicillin base/kg.b.wt.Methods: Twenty-four broiler chickens were divided into two groups. The first group was designed to study the pharmacokinetics of Biocillin®, while the 2nd group was designed to study the pharmacokinetics of Atcomox87%®. Each broiler chicken in both groups was injected intravenously with 20 mg amoxicillin pure standard/kg.b.wt. After 15 days both groups taken orally Biocillin® and Atcomox87%®, respectively. 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, 8, 12 and 24 hours after a single intravenous or oral administration.Results: Amoxicillin in both products obeyed a two compartments open model following I.V. injection. The disposition kinetics of Biocillin® and Atcomox87%® following oral administration of 20 mg amoxicillin base/kg.b.wt. revealed that the maximum blood concentration [Cmax] were 10.79 and 10.30 μg/ml and attained at [tmax] of 0.90 and 0.86 hours, respectively. The mean systemic bioavailability of amoxicillin in Biocillin® and Atcomox 87%® after oral administration in healthy chickens was 64.15 and 65.54%, respectively.Conclusions: Atcomox 87%® is bioequivalent to Biocillin® since the ratios of Cmax, AUC0-24 and AUC0-∞ (T/R) were 0.95, 0.91 and 0.90 respectively. These are within the bioequivalence acceptance range. Biocillin® and Atcomox87%® are therefore bioequivalent and interchangeable.


2020 ◽  
Vol 8 (1) ◽  
pp. 60
Author(s):  
Ashraf Elkomy ◽  
Mohamed Aboubakr

The present study was designed to assess the comparative bio-equivalence of Lincopharm 800® and Lincoyosr® in healthy broiler chicken after oral administration of both products in a dose of 20 mg lincomycin base/kg b.wt. Twenty four broiler chickens were divided into two groups. The first group was designed to study the pharmacokinetics of Lincopharm 800®, while the 2nd group was designed to study the pharmacokinetics of Lincoyosr®. Each broiler chicken in both groups was orally administered with 20 mg lincomycin 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, 8, 12 and 24 hours after a single oral administration. The disposition kinetics of Lincopharm 800® and Lincoyosr® following oral administration of 20 mg lincomycin base /kg b.wt, revealed that the maximum blood concentration of lincomycin [Cmax] were 4.81 and 4.62 μg/ml and attained at [tmax] of 1.36 and 1.35 hours, respectively. In conclusion: Lincoyosr® is bioequivalent to Lincopharm 800® since the ratios of Cmax, AUC0-24 and AUC0-∞ (T/R) was 0.96, 0.92 and 0.91 respectively. These are within the bioequivalence acceptance range. Lincoyosr® and Lincopharm 800® are therefore bioequivalent and interchangeable.   


Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 569
Author(s):  
Huiwen Wang ◽  
Ximin Zeng ◽  
Liu Cao ◽  
Qiang He ◽  
Jun Lin

Enterobactin (Ent) is a highly conserved and important siderophore for the growth of many Gram-negative bacterial pathogens. Therefore, targeting Ent for developing innovative intervention strategies has attracted substantial research interest in recent years. Recently, we developed a novel Ent conjugate vaccine that has been demonstrated to be effective for controlling Gram-negative pathogens using both in vitro and in vivosystems. In particular, active immunization of chickens with the Ent conjugate vaccine elicited strong immune responses and significantly reduced intestinal colonization of Campylobacter jejuni, the leading foodborne bacterial pathogen. Given that hyperimmune egg yolk immunoglobulin Y (IgY) has been increasingly recognized as a promising and practical non-antibiotic approach for passive immune protection against pathogens in livestock, in this study, we assessed the efficacy of oral administration of broiler chickens with the anti-Ent hyperimmune egg yolk powder to control C. jejuni colonization in the intestine. However, supplementation of feed with 2% (w/w) of anti-Ent egg yolk powder failed to reduce C. jejuni colonization when compared to the control group. Consistent with this finding, the ELISA titers of the specific IgY in cecum, ileum, duodenum, gizzard, and serum contents were similar between the two groups throughout the trial. Chicken intestinal microbiota also did not change in response to the egg yolk powder treatment. Subsequently, to examine ex vivo stability of the egg yolk IgY, the chicken gizzard and duodenum contents from two independent sources were spiked with the egg yolk antibodies, incubated at 42 °C for different lengths of time, and subjected to ELISA analysis. The specific IgY titers were dramatically decreased in gizzard contents (up to 2048-fold) but were not changed in duodenum contents. Collectively, oral administration of broiler chickens with the anti-Ent egg yolk powder failed to confer protection against intestinal colonization of C. jejuni, which was due to instability of the IgY in gizzard contents as demonstrated by both in vivo and ex vivo evidence.


1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.


1997 ◽  
Vol 77 (02) ◽  
pp. 376-382 ◽  
Author(s):  
Bruce Lages ◽  
Harvey J Weiss

SummaryThe possible involvement of secreted platelet substances in agonist- induced [Ca2+]i increases was investigated by comparing these increases in aspirin-treated, fura-2-loaded normal platelets and platelets from patients with storage pool deficiencies (SPD). In the presence and absence of extracellular calcium, the [Ca2+]i response induced by 10 µM ADP, but not those induced by 0.1 unit/ml thrombin, 3.3 µM U46619, or 20 µM serotonin, was significantly greater in SPD platelets than in normal platelets, and was increased to the greatest extent in SPD patients with Hermansky-Pudlak syndrome (HPS), in whom the dense granule deficiencies are the most severe. Pre-incubation of SPD-HPS and normal platelets with 0.005-5 µM ADP produced a dose-dependent inhibition of the [Ca2+]i response induced by 10 µ M ADP, but did not alter the [Ca2+]i increases induced by thrombin or U46619. Within a limited range of ADP concentrations, the dose-inhibition curve of the [Ca2+]i response to 10 µM ADP was significantly shifted to the right in SPD-HPS platelets, indicating that pre-incubation with greater amounts of ADP were required to achieve the same extent of inhibition as in normal platelets. These results are consistent with a hypothesis that the smaller ADP-induced [Ca2+]i increases seen in normal platelets may result from prior interactions of dense granule ADP, released via leakage or low levels of activation, with membrane ADP receptors, causing receptor desensitization. Addition of apyrase to platelet-rich plasma prior to fura-2 loading increased the ADP-induced [Ca2+]i response in both normal and SPD-HPS platelets, suggesting that some release of ADP derived from both dense granule and non-granular sources occurs during in vitro fura-2 loading and platelet washing procedures. However, this [Ca2+]i response was also greater in SPD-HPS platelets when blood was collected with minimal manipulation directly into anticoagulant containing apyrase, raising the possibility that release of dense granule ADP resulting in receptor desensitization may also occur in vivo. Thus, in addition to enhancing platelet activation, dense granule ADP could also act to limit the ADP-mediated reactivity of platelets exposed in vivo to low levels of stimulation.


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