Pharmacokinetics of ceftiofur hydrochloride in pigs infected with porcine reproductive and respiratory syndrome virus

Tantituvanont, Angkana; Yimprasert, Walaisiri; Werawatganone, Pornpen; Nilubol, Dachrit

doi:10.1093/jac/dkn496

Cited by 28 publications

(31 citation statements)

References 13 publications

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“…This timing targeted the peak viremia of the wild-type virus, VR-2385, based on previous literature (Johnson et al, 2004). Tantituvanont et al (2009) found similar results with PRRSv challenged pigs and the pharmacokinetics of a shorter acting ceftiofur preparation, ceftiofur hydrochloride. Similar to observations in the present study with CCFA, ceftiofur hydrochloride in PRRSv challenged pigs was reported to have higher Cl/F, higher Vz/F, and lower AUC.…”

Section: Discussionmentioning

confidence: 78%

“…There is a reason to believe that a PRRSv infection could impact absorption, volume of distribution, and clearance. Suggested mechanisms by which a general disease state may alter PK include changes in capillary permeability, hepatic function, renal function, plasma proteins, and vascular pH (Mengelers et al, 1995;Agerso et al, 2000;Post et al, 2002;Riviere, 2009;Tantituvanont et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

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Vaccination mitigates the impact of PRRSv infection on the pharmacokinetics of ceftiofur crystalline‐free acid in pigs

Sparks

Karriker

Day

et al. 2016

Vet Pharm & Therapeutics

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The pharmacokinetics of intramuscularly administered ceftiofur crystalline-free acid (CCFA) were determined in pigs that were clinically healthy (n = 8), vaccinated with a Porcine reproductive and respiratory syndrome modified live virus (PRRS MLV) (n = 10), challenged with wild-type porcine reproductive and respiratory syndrome virus (PRRSv) VR-2385 (n = 10), or vaccinated with PRRS MLV and later challenged with wild-type PRRSv VR-2385 (n = 10). Animals were given a single dose of CCFA intramuscularly at 5 mg/kg body weight. Blood was collected at 0 (pretreatment), 0.25, 0.5, 1, 6, 12, 24, 48, 96, 144, 192, and 240 h postinjection. Plasma was analyzed using liquid chromatography-mass spectrometry. Plasma concentration-time curves for each group were evaluated with noncompartmental modeling. When compared to control animals, those receiving the PRRSv wild-type challenge only had a lower AUC , higher Cl/F, and higher Vz/F. The PRRSv wild-type challenge only group had the longest T . The C did not differ among all four treatments. Control animals had no statistically significant differences from animals vaccinated with PRRS MLV alone or animals vaccinated with PRRS MLV and later challenged with wild-type PRRSv. Our results suggest that PRRSv wild-type infection has the potential to alter CCFA pharmacokinetics and PRRS MLV vaccination may attenuate those changes.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Vaccination mitigates the impact of PRRSv infection on the pharmacokinetics of ceftiofur crystalline‐free acid in pigs

Sparks

Karriker

Day

et al. 2016

Vet Pharm & Therapeutics

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“…Other studies have also shown significantly higher AUC of docetaxel and reduced glomerular filtration rate, suggesting changes in renal CYP in rats injected with the recombinant adenovirus expressing -galactosidase (Le et al, 2006;Wonganan et al, 2009). On the contrary, significantly reduced C max and AUC of ceftiofur hydrochloride were observed in pigs infected with porcine reproductive and respiratory syndrome virus compared to the uninfected pigs (Tantituvanont et al, 2009). …”

Section: Pk/pd Studiesmentioning

confidence: 95%

Altered Drug Metabolism and Transport in Pathophysiological Conditions

Gandhi¹,

Ghose²

2012

Topics on Drug Metabolism

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“…Ceftiofur is the only injectable antimicrobial approved as a daily dosage of 1.1-2.2 mg/kg body weight, by Food and Drug Administration (FDA) in goats for the treatment of respiratory diseases associated with P. multocida and M. haemolytica. Pharmacokinetic properties of ceftiofur have been investigated in cattle (Soback et al, 1991;Erskine et al, 1995;Brown et al, 1996Brown et al, , 2000Okker et al, 2002;von Krueger et al, 2013;Gorden et al, 2016), camel (Goudah, 2007), goat (Courtin et al, 1997;Dore et al, 2011), horse (Collard et al, 2011;Credille et al, 2012;Fultz et al, 2013;Macpherson et al, 2013), sheep Rivera-Garcia et al, 2014), pig (Brown et al, 1999;Tantituvanont et al, 2009;Day et al, 2015) and alpacas (Dechant et al, 2013). Recently, a long-acting formulation of ceftiofur, ceftiofur crystalline-free acid (CCFA) (CCFA-SS; EXCEDE http:// pfizerah.com), has been approved in the United States for the treatment of bovine respiratory disease and foot rot when administered as a single dose of 6.6 mg/kg of body weight.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic characterization of ceftiofur crystalline‐free acid following subcutaneous administration in domestic goats

Waraich

Sidhu

Daundkar

et al. 2016

Vet Pharm & Therapeutics

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Pharmacokinetic (PK)-pharmacodynamic (PD) integration of crystalline ceftiofur-free acid (CCFA) was established in six healthy female goats administered subcutaneously (s.c.) on the left side of the neck at a dosage of 6.6 mg/kg body weight. Serum concentrations of ceftiofur and desfuroylceftiofur (DFC) were determined using high-performance liquid chromatography. Mutant prevention concentration (MPC), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of ceftiofur were determined for Pasteurella (P.) multocida. Mean terminal half-life and mean residence time of ceftiofur + DFC were 48.6 h and 104 h, respectively. In vitro plasma protein binding of ceftiofur was 46.6% in goats. The MIC and MBC values of ceftiofur were similar in serum and MHB and a very small difference between these values confirmed bactericidal activity of drug against P. multocida. In vitro and ex vivo time-kill curves for P. multocida demonstrated a time-dependent killing action of drug. Considering target serum concentration of 0.20 μg/mL, PK-PD values for AUC /MIC and T > MIC , respectively, were 302 h and 192 h against P. multocida. A MPC/MIC ratio of 10-14 indicated that selective pressure for proliferation of resistant mutants of P. multocida is minimal after CCFA single-dose administration. Based on MPC = 1.40 μg/mL for P. multocida, the PK-PD indices, viz. T > MPC and AUC /MPC, were 48 h and 43 h, respectively. The data suggested the use of single dose (6.6 mg/kg, s.c.) of CCFA in goats to obtain clinical and bacteriological cure of pneumonia due to P. multocida.

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Pharmacokinetics of ceftiofur hydrochloride in pigs infected with porcine reproductive and respiratory syndrome virus

Abstract: The pharmacokinetic profile of ceftiofur is altered in PRRSV-infected pigs due to the decreased plasma ceftiofur concentration compared with clinically healthy pigs.

Cited by 28 publications

References 13 publications

Vaccination mitigates the impact of PRRSv infection on the pharmacokinetics of ceftiofur crystalline‐free acid in pigs

Vaccination mitigates the impact of PRRSv infection on the pharmacokinetics of ceftiofur crystalline‐free acid in pigs

Altered Drug Metabolism and Transport in Pathophysiological Conditions

Pharmacokinetic and pharmacodynamic characterization of ceftiofur crystalline‐free acid following subcutaneous administration in domestic goats

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