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

Abstract

Diaveridine (DVD) is widely used for the prevention and treatment of coccidiosis and leucocytozoonosis infections in food-producing animals. To gain a better understanding of DVD metabolism and pharmacokinetics in healthy Landrace/Doric Cross castrated male pigs and both female and male Cobb 500 broiler chickens, a method involving radioactive tracing coupled with LC/MS-IT-TOF was developed for the identification and quantitation of DVD and its metabolites in pig and chicken plasma, and then was applied to investigate DVD pharmacokinetics. A simple MCX solid phase extraction procedure was adopted for sample preparation. After a single oral administration of 3H-DVD (10 mg/kg BW), three radioactive compounds (D0: DVD; D1: 3′-desmethyl-DVD; and D2: monoglucuronide of 3′-desmethyl-DVD) were identified in pig plasma, while only two radioactive compounds (D0 and D2) were identified in chicken plasma. In both species, the Cmax values for all detected compounds were reached at 2 h after dosing. The Cmax order was D2 (1.38 μg/ml) > D0 (0.49 μg/ml) > D1 (0.24 μg/ml) in pigs and D0 (1.55 μg/ml) > D2 (0.27 μg/ml) in chickens. The longer t1/2 (elimination half-life) of D0 contributed to the slow elimination of DVD-related compounds. The t1/2β of D0 in pigs (66.41 h) was significantly longer than that in chickens (48.30 h), but the t1/2 of total DVD-related metabolites in pigs (42.86 h) was lower than that in chickens (56.11 h). These findings suggested that the metabolism and pharmacokinetics of DVD in pigs and chickens were significantly different, and that this would affect its effectiveness, toxicology, and food safety in these animals.

Metabolic insights into HIV/TB co-infection: an untargeted urinary metabolomics approach

“…The elevated levels of 2-hydroxycyclohexane-carboxylic acid, often found in foods and natural products (Wishart et al, 2022 ), reflect the unique dietary habits or the consumption of traditional medicines within the HIV-/TB+ cohort. Similarly, increased levels of diaveridine, an antibacterial agent used in animal feeds (Wang et al, 2022 ), suggest dietary exposure through animal products, with the highest levels in the HIV+/TB+ group indicating altered excretion and processing due to the compounded effects of both HIV and TB.…”

Metabolism and Tissue Elimination of Diaveridine in Swine, Chickens, and Rats Using Radioactive Tracing Coupled with LC–ESI–IT–TOF/MS

“…Compared with that in swine, the weak biotransformation of DVD in chickens indicates that it will have a longer half-life. This presumption was supported by the pharmacokinetic parameters of DVD in the two species. , Only rats were shown to have a sulfonation metabolic pathway of DVD that resulted in the creation of the novel metabolite M5. Meanwhile, metabolite M3 was discovered in chickens and rats, whereas metabolite M4 was discovered in swine and chickens.…”

“…These metabolites were formed via O -demethylation, α-hydroxylation, benzene ring-hydroxylation, N-oxidation, 4′-methylation, NH 2 -glucuronidation, and O -demethylation-glucuronidation . In our previous study, DVD metabolites in pig and chicken plasma were identified by the radioactive tracing coupled with the LC/MS–IT–TOF method, and their kinetic parameters were profiled . However, DVD-related metabolites in excreta, the routes of excretion, mass balance, tissue distribution, and elimination remain unknown.…”

“…15 In our previous study, DVD metabolites in pig and chicken plasma were identified by the radioactive tracing coupled with the LC/MS− IT−TOF method, and their kinetic parameters were profiled. 16 However, DVD-related metabolites in excreta, the routes of excretion, mass balance, tissue distribution, and elimination remain unknown. Thus, the safety of DVD applications is questionable.…”