Pharmacokinetics and pharmacodynamics of gamithromycin in pulmonary epithelial lining fluid in naturally occurring bovine respiratory disease in multisource commingled feedlot cattle.

The objectives of this study were to determine (i) whether an association exists between individual pharmacokinetic parameters and treatment outcome when feeder cattle were diagnosed with bovine respiratory disease (BRD) and treated with gamithromycin (Zactran(®) ) at the label dose and (ii) whether there was a stronger association between treatment outcome and gamithromycin concentration in plasma or in the pulmonary epithelial lining fluid (PELF) effect compartment. The study design was a prospective, blinded, randomized clinical trial utilizing three groups of 60 (362-592 lb) steers/bulls randomly allocated within origin to sham injection or gamithromycin mass medication. Cattle were evaluated daily for signs of BRD by a veterinarian blinded to treatment. Animals meeting the BRD case definition were enrolled and allocated to a sample collection scheme consisting of samples for bacterial isolation (bronchoalveolar lavage fluid and nasopharyngeal swabs) and gamithromycin concentration determination (PELF and plasma). Gamithromycin susceptibility of M. haemolytica (n = 287) and P. multocida (n = 257) were determined using broth microdilution with frozen panels containing gamithromycin at concentrations from 0.03 to 16 µg/mL. A two-compartment plasma pharmacokinetic model with an additional compartment for gamithromycin in PELF was developed using rich data sets from published and unpublished studies. The sparse data from our study were then fit to this model using nonlinear mixed effects modeling to estimate individual parameter values. The resulting parameter estimates were used to simulate full time-concentration profiles for each animal in this study. These profiles were analyzed using noncompartmental methods so that PK/PD indices (AUC24 /MIC, AUC∞ /MIC, CMAX /MIC) could be calculated for plasma and PELF (also T>MIC) for each individual. The calculated PK/PD indices were indicative that for both M. haemolytica and P. multocida a higher drug exposure in terms of concentration, and duration of exposure relative to the MIC of the target pathogen, was favorable to a successful case outcome. A significant association was found between treatment success and PELF AUC0-24 /MIC for P. multocida. The calves in this study demonstrated an increased clearance and volume of distribution in plasma as compared to the healthy calves in two previously published reports. Ultimately, the findings from this study indicate that higher PK/PD indices were predictive of positive treatment outcomes.

Sensitivity and specificity of serum copper determination for detection of copper deficiency in feeder calves.

OBJECTIVE: To determine the relationship between serum and liver copper concentrations and evaluate serum copper determination for diagnosis of copper deficiency in juvenile beef calves. DESIGN: Cross-sectional study. ANIMALS: 105 juvenile beef calves. PROCEDURE: Copper concentrations were measured in paired liver and serum samples from 6- to 9-month-old beef calves. Regression models that predicted liver copper concentration as a function of serum copper concentration were developed. Sensitivity and specificity of serum copper concentration for detection of low liver copper concentration were determined, using a range of serum copper concentrations as test endpoints. Positive and negative predictive values were calculated. RESULTS: The association between serum and liver copper concentrations was significant; however, regression models accounted for only a small portion of the variation in liver copper concentrations. For a serum copper concentration endpoint of 0.45 microg/g, sensitivity and specificity for detection of low liver copper concentration were 0.53 and 0.89, respectively. Positive and negative predictive values of serum copper concentration for detection of low liver copper concentration ranged from 0.37 to 0.85 and 0.63 to 0.94, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Regression models are inappropriate for predicting copper status as a function of serum copper concentration. Serum copper concentration is fairly specific for detection of low liver copper concentration but only marginally sensitive when serum copper concentration of 0.45 microg/g is used as a test endpoint. The value of serum copper concentration as a diagnostic indicator depends on prevalence of copper deficiency.

Use of age and serum gamma-glutamyltransferase activity to assess passive transfer status in lambs.

OBJECTIVE: To develop an algorithm for predicting passive transfer status of lambs of various ages, using the lamb's age and serum gamma-glutamyltransferase (GGT) activity. DESIGN: Prospective study. ANIMALS: 51 Suffolk, Columbia, and crossbred lambs from 1 to 16 days old. PROCEDURE: Serum was obtained from all lambs. Serum GGT activity was measured, using a commercially available kit. Serum IgG concentration was determined by use of radial immunodiffusion. Day-1 serum IgG concentration was estimated from sample IgG concentration, lamb age, and the published 14-day half-life of IgG in lambs. Stepwise multivariate regression models were developed to estimate day-1 serum IgG concentration as a function of the natural logarithm of serum GGT activity (In[GGT]) and natural logarithm of lamb age (In[age]) at the time of sampling. These regression models were then used to calculate serum GGT activities that were equivalent to various day-1 IgG concentrations in lambs of various ages. RESULTS: In(GGT) and In(age) were significantly associated with estimated day-1 IgG concentration. Day-1 serum IgG concentration could be predicted using the formula: IgG = -7,686 + 1,366(In[GGT]) + 1,199(In[age]). The model was moderately accurate in predicting serum IgG concentration (R2 = 0.52). CLINICAL IMPLICATIONS: Serum GGT activity can be used to assess passive transfer status of lambs.