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Disposition following single intravenous injection (2 mg/kg) and pharmacodynamics of cefquinome were investigated in buffalo calves 6-8 months of age. Drug levels in plasma were estimated by high-performance liquid chromatography. The plasma concentration-time profile following intravenous administration was best described by a two-compartment open model. Rapid distribution of cefquinome was evident from the short distribution half-life (t ½ α = 0.36 ± 0.01 h), and small apparent volume of distribution (Vd area = 0.31 ± 0.008 L/kg) indicated limited drug distribution in buffalo calves. The values of area under plasma concentration-time curve, elimination half-life (t ½ β ), total body clearance (ClB), and mean residence time were 32.9 ± 0.56 μg · h/mL, 3.56 ± 0.05 h, 60.9 ± 1.09 mL/h/kg, and 4.24 ± 0.09 h, respectively. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration of cefquinome were 0.035-0.07 and 0.05-0.09 μg/mL, respectively. A single intravenous injection of 2 mg/kg may be effective to maintain the MIC up to 12 h in buffalo calves against the pathogens for which cefquinome is indicated.

The pharmacokinetic-pharmacodynamic (PK/PD) modeling of enrofloxacin data using mutant prevention concentration (MPC) of enrofloxacin was conducted in febrile buffalo calves to optimize dosage regimen and to prevent the emergence of antimicrobial resistance. The serum peak concentration (Cmax ), terminal half-life (t1/2 K10) , apparent volume of distribution (Vd(area) /F), and mean residence time (MRT) of enrofloxacin were 1.40 ± 0.27 μg/mL, 7.96 ± 0.86 h, 7.74 ± 1.26 L/kg, and 11.57 ± 1.01 h, respectively, following drug administration at dosage 12 mg/kg by intramuscular route. The minimum inhibitory concentration (MIC), minimum bactericidal concentration, and MPC of enrofloxacin against Pasteurella multocida were 0.055, 0.060, and 1.45 μg/mL, respectively. Modeling of ex vivo growth inhibition data to the sigmoid Emax equation provided AUC24 h /MIC values to produce effects of bacteriostatic (33 h), bactericidal (39 h), and bacterial eradication (41 h). The estimated daily dosage of enrofloxacin in febrile buffalo calves was 3.5 and 8.4 mg/kg against P. multocida/pathogens having MIC90 ≤0.125 and 0.30 μg/mL, respectively, based on the determined AUC24 h /MIC values by modeling PK/PD data. The lipopolysaccharide-induced fever had no direct effect on the antibacterial activity of the enrofloxacin and alterations in PK of the drug, and its metabolite will be beneficial for its use to treat infectious diseases caused by sensitive pathogens in buffalo species. In addition, in vitro MPC data in conjunction with in vivo PK data indicated that clinically it would be easier to eradicate less susceptible strains of P. multocida in diseased calves.

Objectives: To conduct a toxicological risk assessment of di(2-ethylhexyl) phthalate (DEHP) in cardiac catheter (CC) set, following a chemical characterization study and systematic review of toxicity literature. Methods: CC set was subjected to chemical analysis study for estimation of DEHP in the PVC containing parts using HPLC-PDA. Toxicity literature on DEHP was collected from online database literature search and reports of international monitoring bodies. From the existing knowledge of DEHP toxicity, tolerable intake for humans was derived from the critical toxicity endpoint. This was compared to the levels of DEHP in CC to make scientific judgement on this risk to patients. Findings: During clinical use of medical devices like CC tubing set, intravenous infusion set, storage of blood in blood bags there is a possibility of DEHP leaching in to the patient body via fluids or blood. Based on the chemical analysis of device extract, the content of DEHP in the CC tubing set was estimated to be 38.18 mg per device. The patient exposure of DEHP was calculated assuming clinical use of one device per day. Review of extensive toxicity literature revealed the critical toxicity endpoints of DEHP toxicity. Activation of peroxisome proliferatoractivated receptor alpha (PPAR-α) in rodents leading to hepatic tumors and disruption of normal endocrine function of gonads are the primary concerns of toxicity. Human tolerable exposure derived from the NOAEL obtained from a key reproductive toxicity study was used to evaluate the toxicological risk of DEHP. From the assessment, the level of DEHP leaching out from the CC tubing set is concluded to be safe in humans. Novelty: This manuscript describes a method for risk assessing DEHP toxicity in medical devices using a case study of CC set. This approach is based on generating patient exposure using chemical analysis and comparing this with toxicology data from literature to make informed decisions on patient safety.

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