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- Author or Editor: Nicholas K. Van Engen x
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Abstract
OBJECTIVE To determine the effect of age on the pharmacokinetics and pharmacodynamics of flunixin meglumine following IV and transdermal administration to calves.
ANIMALS 8 healthy weaned Holstein bull calves.
PROCEDURES At 2 months of age, all calves received an injectable solution of flunixin (2.2 mg/kg, IV); then, after a 10-day washout period, calves received a topical formulation of flunixin (3.33 mg/kg, transdermally). Blood samples were collected at predetermined times before and for 48 and 72 hours, respectively, after IV and transdermal administration. At 8 months of age, the experimental protocol was repeated except calves received flunixin by the transdermal route first. Plasma flunixin concentrations were determined by liquid chromatography-tandem mass spectroscopy. For each administration route, pharmacokinetic parameters were determined by noncompartmental methods and compared between the 2 ages. Plasma prostaglandin (PG) E2 concentration was determined with an ELISA. The effect of age on the percentage change in PGE2 concentration was assessed with repeated-measures analysis. The half maximal inhibitory concentration of flunixin on PGE2 concentration was determined by nonlinear regression.
RESULTS Following IV administration, the mean half-life, area under the plasma concentration-time curve, and residence time were lower and the mean clearance was higher for calves at 8 months of age than at 2 months of age. Following transdermal administration, the mean maximum plasma drug concentration was lower and the mean absorption time and residence time were higher for calves at 8 months of age than at 2 months of age. The half maximal inhibitory concentration of flunixin on PGE2 concentration at 8 months of age was significantly higher than at 2 months of age. Age was not associated with the percentage change in PGE2 concentration following IV or transdermal flunixin administration.
CONCLUSIONS AND CLINICAL RELEVANCE In calves, the clearance of flunixin at 2 months of age was slower than that at 8 months of age following IV administration. Flunixin administration to calves may require age-related adjustments to the dose and dosing interval and an extended withdrawal interval.
Abstract
OBJECTIVE
To compare immune responses induced by 2 commercially available vaccines with a bovine herpesvirus type 1 (BHV1) component following intranasal (IN) administration to colostrum-fed calves.
ANIMALS
90 male Holstein calves (ages, 5 to 14 days).
PROCEDURES
In a randomized complete block design, each calf received 2 mL (1 mL/nostril) of vaccine A (n = 30), vaccine B (30), or saline (0.9% NaCl) solution (30) on day 0. Blood samples were collected for determination of serum anti-BHV1 IgG titer, and nasal fluid (NF) samples were collected for determination of interferon (IFN)-α and IFN-γ concentrations and for secretory IgA titers against BHV1, Mannheimia haemolytica, and Pasteurella multocida at predetermined times for 42 days after vaccination.
RESULTS
All calves were seropositive for anti-BHV1 IgG, and the mean anti-BHV1 IgG titer did not differ significantly among the 3 groups at any time. Both vaccines induced significant transient increases in NF IFN-α and IFN-γ concentrations. On day 5, mean IFN-α concentration and the proportion of calves with detectable IFN-α concentrations for the vaccine A group were significantly greater than those for the vaccine B and control groups. On day 42, the mean NF anti–P multocida IgA titers for both vaccine groups were significantly greater than that of the control group.
CONCLUSIONS AND CLINICAL RELEVANCE
Both vaccines induced innate and acquired immune responses in calves with colostral antibodies. The magnitude of the IFN-α response and proportion of calves with detectable IFN-α differed between the 2 vaccine groups. Both vaccines appeared to enhance the IgA response against P multocida.
