ABSTRACT
Our objective was to determine the influence of season (winter, spring, summer, and fall) on travel patterns, hoof growth, and longissimus dorsi muscle (LM) height and fat thickness between 13th and 14th ribs in 16 horses aged <4 years (eight males and eight females) of Morgan, Quarter Horse, and Moriesian breeds. Real-time ultrasound images of LM height and fat thickness as well as measures of hoof growth were obtained at the end of each season. Global positioning system tracking was conducted for four randomly selected days and one storm day in each season. Data were analyzed using a linear mixed model procedure in SAS. Season influenced fat deposition (P < .01) with the greatest increase in fall (P < .05) but had minimal effect on muscle growth. Hoof growth was greatest in summer and least in winter (P < .01). The average distance traveled was greater in spring and summer than in fall and winter (P < .01). The horses moved for less time and traveled less distance on storm days (P < .05) compared with nonstorm days. Young horses also traveled less on storm days, which indicates that it may be especially important to provide shelter for them. It was concluded that season influenced fat deposition, distance traveled, and hoof growth of domestic young horses. A better understanding of these factors could help equine professionals manage young horses more efficiently to benefit the horses' physical well-being.
Subject(s)
Hoof and Claw , Animals , Female , Horses , Male , Muscles , SeasonsABSTRACT
Variability in oral absorption in pre-clinical species makes human dose projection challenging. In this study, we investigated the mechanistic basis of variability in oral absorption of a model hydrophobic compound with pH-dependent solubility, BMS-955829, after oral dosing in rats, dogs, and cynomolgus monkeys. The contribution of regional absorption to pharmacokinetic variability was assessed in ported monkeys by direct intraduodenal and intraileal administration. The effect of BMS-955829 on gastric emptying and intestinal motility was investigated by radiography after co-administration of barium. BMS-955829 exhibited species dependent oral bioavailability, with high variability in monkeys. During regional absorption studies, highest rate of drug absorption was observed after direct intraduodenal administration. Radiography studies indicated that BMS-955829 slowed gastric emptying and intestinal motility. The effect of rate and site of drug release on oral exposure was studied using different drug product formulations. Reducing the rate of drug release reduced oral exposure variability without compromising exposure in cynomolgus monkeys. This effect was likely mediated by avoidance of rapid initial absorption and drug effect on gastric emptying and intestinal transit within the biorelevant timeframe. Thus, drug release rate can modulate the effect of physiological factors on variability in the oral absorption of sensitive compounds.
