Detection, quantifications, and pharmacokinetics of ponazuril in healthy swine

Abstract

A study on pharmacokinetics of ponazuril in piglets was conducted after a single oral dose of 5.0 mg/kg b.w. Plasma concentrations were measured by high-performance liquid chromatography assay with UV detector at 255-nm wavelength. Pharmacokinetic parameters were derived by use of a standard noncompartmental pharmacokinetic analysis. Samples from six piglets showed good plasma concentrations of ponazuril, which peaked at 5.83 ± 0.94 μg/mL. Mean ± SD area under the plasma concentration-time curve was 1383.42 ± 363.26 h/μg/mL, and the elimination half-life was 135.28 ± 19.03 h. Plasma concentration of ponazuril peaked at 42 h (range, 36-48 h) after administration and gradually decreased but remained detectable for up to 33 days. No adverse effects were observed during the study period. The results indicate that ponazuril was relatively well absorbed following a single dose, which makes ponazuril likely to be effective in swine.

Identification of Novel Positive Allosteric Modulators of Neurotrophin Receptors for the Treatment of Cognitive Dysfunction

“…The fact that ACD855 (Ponazuril) has been used as a safe and well tolerated veterinary medicine for long time [62,83] has made it a suitable candidate for repurposing in humans as a cognitive enhancer. The compound was able to facilitate LTP in a manner that is similar to BDNF itself and increased the levels of acetylcholine in the ventral hippocampus, suggesting that ACD855 can have an effect on both glutamatergic synaptic function as well as cholinergic function.…”

Pharmacokinetics of orally administered single‐dose ponazuril in cats

“…Ponazuril, (1‐methyl‐3‐[3‐methyl‐4‐(4‐trifluoromethanesulfonyl‐phenoxy)‐phenyl]‐[1,3,5]‐triaziane‐2,4,6‐trione), is a triazine derivative coccidiocidal drug that has been studied in numerous species including swine, llamas, cattle, goats, horses, and dogs. (Charles et al., 2007; Dirikolu et al., 2009; Furr & Kennedy, 2000; Love et al., 2015; Prado et al., 2011; Zou et al., 2014) It is available in the United States as Marquis ® Paste, and is labeled to treat Sarcocystis neurona infection in horses. Ponazuril is an effective anti‐coccidial medication in chickens, calves, and buffalo.…”

“…These time points were chosen based on clearance times observed in other species. (Dirikolu et al., 2009; Prado et al., 2011; Zou et al., 2014) Most samples consisted of 1ml of blood; no more than 24 ml of blood was taken from one cat over the 2 week period. For samples taken via catheter, a 3 ml sample was withdrawn prior to collection of the sample for testing, which was returned prior to flushing the catheter to limit the total volume of blood removed from each cat.…”

Bioanalytical RP‐HPLC method for the determination of ponazuril in plasma

“…Ponazuril concentrations have been determined by MS (Love et al, 2015;Olsen et al, 2012), HPLC using fluorescent detection (Furr & Kennedy, 2001, 2020 and HPLC with ultraviolet (UV) detection (Dirikolu, Karpiesiuk, et al, 2009;Dirikolu et al, 2012;Dirikolu, Yohn, et al, 2009;Zou et al, 2014). Some UV methods require 1 mL of sample and require a pH adjustment prior to a complex solid-phase extraction protocol (Dirikolu, Karpiesiuk, et al, 2009;Dirikolu, Yohn, et al, 2009;Dirikolu et al, 2012).…”

“…The recovery of these methods was only 88%. Another method requires a 1 mL sample divided in half and extracted two times (Zou et al, 2014). This method had a curve range of only 0.1-10 μg/mL and a runtime of 20 min.…”