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

Abstract

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.

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

“…However, we often overlook the antibacterial activity of the drug metabolites, which is a critical factor in formulating dosage regimen. Twelve metabolites of ADP can be detected in swine, broilers, carp and rats, and A 1 and A 2 , which occupied 11.4% and 11.8% in swine, 12.8% and 14.0% in broilers, respectively, were the two main metabolites in these edible tissues 25 . In this study, the in vitro activities of A 1 and A 2 on Streptococcus from swine and Salmonella from chickens were equal to those of ADP.…”

“…ADP can be metabolized into 11, 9, 2 and 2 metabolites in swine, broilers, carp and rats, respectively, and N -monodesmethyl-ADP (A 1 ) and N -didesmethyl-ADP (A 2 ) are the main metabolites in their edible tissues 25 . In sheep, A 1 and A 2 also appear to be equally important metabolites 26 .…”

Generic Hapten Synthesis, Broad-Specificity Monoclonal Antibodies Preparation, and Ultrasensitive ELISA for Five Antibacterial Synergists in Chicken and Milk

“…ASGs are commonly used in combination with sulfonamides or other antimicrobials, such as fluoroquinolones, β-lactams, and aminoglycosides, and are efficient in inhibiting Gram-positive and Gram-negative bacteria. − To date, the ASG family consists of nine drugs, including trimetho­prim (TMP), diaveridine (DVD), brodimo­prim (BOP), ormeto­prim (OMP), baquilo­prim (BQP), tetroxo­prim (TXP), metio­prim (MTP), adito­prim (ADP), and iclaprim (ICL). Of these ASGs, ADP and DVD are exclusively used in animals, while ICL is used in humans, and the remainder are both human and veterinary medicines. ,− DVD, OMP, and especially TMP are the most commonly used medicines in animal husbandry for the treatment of bacterial and protozoal diseases . For example, compounds of TMP/sulfa­diazine are used for urinary, gastro­intestinal, and respiratory tract infections, and compounds of DVD/sulfa­quinoxaline are used for anti­protozoal drugs in food animals …”

Metabolite Identification and Pharmacokinetic Behavior of Diaveridine in the Plasma of Pigs and Chickens Based on Radioactive Tracing Coupled With LC/MS-IT-TOF Assay

“…The total radioactivity assay was conducted in accordance with a previous study with a few modifications ( 20 ). Briefly, 50 μl of plasma was mixed with 50 μl of 0.1 mol/L EDTA-Na and 50 μl of 30% H 2 O 2 at 50°C in a shaking water bath for 2 h for bleaching.…”