Pharmacokinetics and pharmacodynamics of xylazine administered by the intravenous or intra-osseous route in adult horses.

In certain situations, an alternate route for parenteral drug administration in horses may be useful. The intra-osseous (IO) route may provide a safe alternative to the intravenous (i.v.) route for administration of sedatives to horses when the i.v. route is inaccessible or undesirable. Six adult horses were administered xylazine i.v. or IO in a block-randomized crossover design. For the i.v. trial, both jugular veins were catheterized, and one was used for xylazine administration, while the other was used for blood collection. For the IO trial, one jugular vein was catheterized for blood collection and an intra-osseous device was placed in the tuber coxae using a powered driver for xylazine administration. Heart rate, respiratory rate, and head position were measured, and concentration of sedation was assessed at various times up to 90 min. Xylazine concentrations were measured using high-performance liquid chromatography and noncompartmental analysis was performed. General linear mixed modeling and Wilcoxon signed-rank tests were used for statistical analysis, with P ≤ 0.05. There were no significant differences in heart rate, respiratory rate, head position, concentration of sedation, Cmax , Tmax , half-life, or AUC between the i.v. and the IO routes of drug administration. No complications were observed following placement of the intra-osseous device. Intra-osseous xylazine administration provides a useful option in emergent and other settings in which i.v. access is difficult or contraindicated.

Sputum eosinophilia after asthmatic responses induced by isocyanates in sensitized subjects.

To assess the nature and the time-course of the cellular component of airway inflammation induced by isocyanates, we examined nine subjects with occupational asthma induced by toluene- or methylene diphenyl-diisocyanate (TDI, MDI) and four control subjects never exposed to isocyanates. Sputum was induced by inhalation of ultrasonically nebulized hypertonic saline (3-4% NaCl) before and 8, 24, 48 h after inhalation challenge with TDI or MDI. Expectorated samples were incubated with dithiothreitol, washed and cytocentrifuged. Differential cell counts were obtained on slides stained with May-Grünwald-Giemsa. Metachromatic cells (mast cells and basophils) were counted on slides stained with toluidine blue at pH 0.1. One occupational asthmatic exhibited a dual reaction to TDI, two exhibited a single early asthmatic reaction to MDI, six exhibited a late asthmatic reaction to TDI (n = 5) or MDI (n = 1), whereas no reactions were observed in control subjects after TDI challenge. In sensitized subjects eosinophils increased from a median value (interquartile range) of 5 (15)% before challenge to 29 (29)% (P = 0.014) and to 30 (31)% (P = 0.031) 8 and 24 h after TDI/MDI challenges, respectively. Sputum eosinophilia was observed both in early and late reactors and declined to near to baseline values 48 hr after challenge. Percentages of eosinophils in control subjects did not exceed 7% during the study.(ABSTRACT TRUNCATED AT 250 WORDS)