Comparative pharmacokinetics of diaveridine in pigs and chickens following single intravenous and oral administration

Abstract

Comparative pharmacokinetic profiles of diaveridine following single intravenous and oral dose of 10 mg/kg body weight in healthy pigs and chickens were investigated, respectively. Concentrations of diaveridine in plasma samples were determined using a validated high-performance liquid chromatography-ultraviolet (HPLC-UV) method. The concentration-time data were subjected to noncompartmental kinetic analysis by WinNonlin program. The corresponding pharmacokinetic parameters in pigs or chickens after single intravenous administration were as follows, respectively: t (elimination half-life) 0.74 ± 0.28 and 3.44 ± 1.07 h; V (apparent volume of distribution) 2.70 ± 0.99 and 3.86 ± 0.92 L/kg; Cl (body clearance) 2.59 ± 0.62 and 0.80 ± 0.14 L/h/kg; and AUC (area under the blood concentration vs. time curve) 4.11 ± 1.13 and 12.87 ± 2.60 μg∙h/mL. The corresponding pharmacokinetic parameters in pigs or chickens after oral administration were as follows, respectively: t 1.78 ± 0.41 and 2.91 ± 0.57 h; C (maximum concentration) 0.43 ± 0.24 and 1.45 ± 0.57 μg/mL; T (time to reach C ) 1.04 ± 0.67 and 3.25 ± 0.71 h; and AUC 1.33 ± 0.55 and 9.28 ± 2.69 μg∙h/mL. The oral bioavailability (F) of diaveridine in pigs or chickens was determined to be 34.6% and 72.2%, respectively. There were significant differences between the pharmacokinetics profiles in these two species.

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

“…Using an HPLC-UV method, the C max values for DVD were similar (0.43 and 1.45 μg/ml in pigs and chickens, respectively, in previous studies), but the T max values were slightly different (1.04 and 3.25 h in pigs and chickens in previous studies). Moreover, in the present study, the t 1/2 values for DVD in the two species were significantly longer than those of a previous study ( 15 ). These distinctions were probably related to the different sample collection time points as well as the different types of analytical methods used in the two investigations.…”

“…Detection ability of the high-performance liquid chromatography–ultraviolet (HPLC-UV) method is limited. For example, DVD was detected at 168 h in pig and chicken plasma in our study, whereas it was only detected at 6 h in pigs and at 24 h in chickens using a HPLC-UV by Li et al ( 15 ). Although radioactive tracing has sufficient sensitivity for metabolite discovery and quantification, the accuracy of quantification is questionable owing to the absence of reference standards.…”

“…The results showed that the method was sensitive and reliable, and a total of four radiolabeled compounds were identified from this in vivo experiment, of which two were new metabolites ( 14 ). Recently, a comparative pharmacokinetic study of DVD in pigs and chickens was reported following a single intravenous or oral administration ( 15 ). However, only the parent drug DVD was detected, and the data did not reveal the pharmacokinetic behaviors of any DVD-related compounds or the individual pharmacokinetic characteristics of its metabolites.…”

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.…”

“…In the pharmacokinetic study of DVD in pigs and chickens by Li et al. (2017), the dosages were 10 mg/kg b.w . According to VICH GL46, the dose should be in the highest intended treatment concentration .…”