Research Note: Pharmacokinetics of Aditoprim in Turkeys After Intravenous and Oral Administration

Engeli, J; Riond, J.‐L.; Wanner, M.

doi:10.3382/ps.0720979

Cited by 7 publications

(4 citation statements)

References 17 publications

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“…ADP has excellent pharmacokinetic characteristics. Previous studies have shown that ADP has longer elimination half lives (3.3~14.8 h) and higher distribution volumes (4.6~10.4 L/kg) than those of TMP in pig, calf, monkey, sheep and some other animal species 5 6 7 8 9 10 11 12 13 14 15 16 17 , and a similar pattern is observed for ADP where the distribution volume is about four times higher than that of TMP. For the poor pharmacokinetics 18 and the development of antibacterial resistance 19 20 21 , TMP is often used in combination with sulfonamides as antibacterial synergist for the treatment and prevention of bacterial infections in veterinary and human medicine 22 .…”

supporting

confidence: 55%

The antibacterial activities of aditoprim and its efficacy in the treatment of swine streptococcosis

Cheng

Zhu

et al. 2017

Sci Rep

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Aditoprim (ADP) has potential use as an antimicrobial agent in animals. However, its pharmacodynamic properties have not been systematically studied yet. In this study, the in vitro antibacterial activities of ADP and its main metabolites were assayed, and the in vivo antibacterial efficacy of ADP for the treatment of swine streptococcosis was evaluated. It was shown that Salmonella and Streptococcus from swine, Escherichia coli and Salmonella from chickens, E. coli, Streptococcus, Mannheimia, Pasteurella from calves, Streptococcus and Mannheimia from sheep, and E. coli, Flavobacterium columnare, Acinetobacter baumannii and Yersinia ruckeri from fishes were highly susceptible to ADP. Haemophilus parasuis from swine, Staphylococcus aureus, Aeromonas punctate, Mycobacterium tuberculosis, Streptococcus agalactiae from fishes, and Klebsiella from calves and sheep showed moderate susceptibility to ADP, whereas E. coli, Actinobacillus pleuropneumonia, Pasteurella, S. aureus, Clostridium perfringens from swine, S. aureus, C. perfringens from chickens, and S. aureus from calves were resistant to ADP. The main metabolites of ADP showed equal activity to that of their parent compound, and the prevention and therapeutic dosages of ADP recommended for swine streptococcosis were 10 and 20~40 mg/kg b.w., respectively. This study firstly showed that ADP had strong antibacterial activity and had potential to be used as a single drug in the treatment of bacterial infectious diseases.

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supporting

confidence: 55%

The antibacterial activities of aditoprim and its efficacy in the treatment of swine streptococcosis

Cheng

Zhu

et al. 2017

Sci Rep

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“…It is reported that this compound is particularly active against Enterobacteriaceae , Haemophilus , Staphylococcus , Streptococcus , Vibrio , and Aeromonas 2 . Moreover, ADP provides significant pharmacokinetic advantages, including long half-lives (6.1–11.9 h) and high tissue distribution volume (4.4–12.2 L/kg) in various animal species such as sheep 3 4 5 , cattle 6 7 8 9 , pig 10 , horse 11 , turkey 12 , dog 13 , and monkey 14 . These earlier studies have shown that ADP had a good efficacy when administered alone or combined with sulfonamides in a one-day dose for the treatment of respiratory and gastro-intestinal infections.…”

mentioning

confidence: 99%

Metabolism and Disposition of Aditoprim in Swine, Broilers, Carp and Rats

Wang

Huang

Pan

et al. 2016

Sci Rep

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Aditoprim (ADP) is a newly developed antibacterial agent in veterinary medicine. The metabolism and disposition of ADP in swine, broilers, carp and rats were investigated by using a radio tracer method combined with a radioactivity detector and a liquid chromatography/ion trap/time-of-flight mass spectrometry. After a single oral administration, more than 94% of the dose was recovered within 14 d in the four species. The urine excretion was dominant in swine and rats, making up 78% of the dose. N-monodesmethyl-ADP, N-didesmethyl-ADP, and 10 new metabolites were characterized. These metabolites were biotransformed from the process of demethylation, α-hydroxylation, N-oxidation, and NH2-glucuronidation. After an oral dose for 7 d, ADP-derived radioactivity was widely distributed in tissues, and high concentrations were especially observed in bile, liver, kidney, lung, and spleen. The radioactivity in the liver was eliminated much more slowly than in other tissues, with a half-life of 4.26, 3.38, 6.69, and 5.21 d in swine, broilers, carp, and rats, respectively. ADP, N-monodesmethyl-ADP, and N-didesmethyl-ADP were the major metabolites in edible tissues. Notably, ADP was detected with the highest concentration and the longest duration in these tissues. These findings indicated that ADP is the marker residue and the liver is the residue target tissue.

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“…PK studies have shown that ADP has the characteristics of wide distribution in the body, large apparent volume, the long half-life, high bioavailability, etc. It can be used as an alternative to TMP and has broad market prospects [ 22 , 25 , 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Dosing Regimen of Aditoprim and Sulfamethoxazole Combination for the Glaesserella parasuis Containing Resistance and Virulence Genes

Huang

Zhang

et al. 2022

Pharmaceutics

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Glaesserella parasuis (G. parasuis) causes Glasser’s disease in pigs and causes high mortality in piglets. The new drug Aditoprim (ADP) alone or combined with Sulfamethoxazole (SMZ) is one of the good choices for treating respiratory infections. The objective of this study was to recommend the optimal dosing regimen for the treatment of G. parasuis infection which contains resistance and virulence genes by ADP/SMZ compound through pharmacokinetics–pharmacodynamics (PK-PD) modeling. The whole genome of the virulent strain G. parasuis H78 was obtained and annotated by whole genome sequencing. The results show that G. parasuis H78 consists of a unilateral circular chromosome with prophages in the genome. The annotation results of G. parasuis H78 showed that the genome contained a large number of virulence-related genes and drug resistance-related genes. The in vitro PD study showed that the antibacterial effect of ADP/SMZ compound against G. parasuis was time-dependent, and AUC/MIC was selected as the PK-PD modeling parameter. The PK study showed that the content of ADP/SMZ compound in pulmonary epithelial lining fluid (PELF) was higher than plasma, and there were no significant differences in ADP and SMZ PK parameters between the healthy and infected group. The dose equation to calculate the optimal dosing regimen of ADP/SMZ compound administration for control of G. parasuis infection was 5/25 mg/kg b.w., intramuscular injection once a day for 3~5 consecutive days. The results of this study provide novel therapeutic options for the treatment of G. parasuis infection to decrease the prevalence and disease burden caused by G. parasuis.

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Research Note: Pharmacokinetics of Aditoprim in Turkeys After Intravenous and Oral Administration

Cited by 7 publications

References 17 publications

The antibacterial activities of aditoprim and its efficacy in the treatment of swine streptococcosis

The antibacterial activities of aditoprim and its efficacy in the treatment of swine streptococcosis

Metabolism and Disposition of Aditoprim in Swine, Broilers, Carp and Rats

Dosing Regimen of Aditoprim and Sulfamethoxazole Combination for the Glaesserella parasuis Containing Resistance and Virulence Genes

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