PubMed · 15237074
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John DiTraglia. 2004. Bronchiolitis.. https://doi.org/10.1001/archpedi.158.7.707-a
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While resistance exercise (REX) reduces ankle extensor (AE) mass and strength deficits during short-term unloading; additional treatments, concurrently administered with REX, are required to attenuate the greater losses seen with longer unloading periods. Subjects performed left leg REX, which otherwise refrained from ambulatory and weight-bearing activity for 40 days, while randomized to a capsule (placebo, albuterol) dosing regimen with no crossover to note whether albuterol helps REX mitigate unloading-induced AE losses. A third group of subjects served as unloaded controls. On days 0, 20, and 40, the following data were collected from the left leg: calf cross-sectional area and AE strength measures. Cross-sectional area was estimated using anthropometric methodology, whereas AE strength data were obtained from eight unilateral calf-press repetitions on an inertial-based REX device. Repeated-measures mixed-factorial 3 x 3 analyses of covariance, with day 0 values as a covariate, revealed group x time interactions for the strength variables eccentric total work (ETW) and average power (EAP). Tukey's honestly significant difference shows REX-placebo subjects incurred significant ETW and EAP losses by day 40, whereas the REX-albuterol treatment evoked strength gains to those same variables without concurrent muscle accretion. Corresponding concentric variables did not display similar changes. Day 40 control data significantly declined for many variables; relative to the REX-albuterol treatment, some losses were significant after 20 days. ETW and EAP gains to unloaded AE may be due to one or more mechanisms. Continued research identifying mechanisms responsible for such changes, as well as the safety of REX-albuterol administration in other models, is warranted.
Suitable HPLC methods for the direct separation of bambuterol and albuterol enantiomers were developed. The enantioseparation was tested on numerous commercial chiral HPLC columns. For bambuterol the most convenient separation was determined on amylose Chiralpak AD column, and for albuterol on vancomycine Chirobiotic V column. The mobile phase compositions were systematically studied to obtain the optimal chromatographic methods. Validation of methods in selected conditions shows that the chosen methods are selective and precise with linear response of detector for both pairs of enantiomers.
The impact of intestinal conjugative metabolism on oral bioavailability was assessed by sequential and simultaneous analyses of the reported data in humans. The data were retrieved from reports on drugs that are metabolized by sulfate conjugation, and the organ availabilities affecting oral bioavailability were differentiated. Sequential analysis gave the following results. The intestinal availability (Fg) of salbutamol was 0.700, whereas hepatic availability (Fh) and bioavailability (F) were 0.893 and 0.493, respectively. Fg of (+)-terbutaline, (-)-terbutaline, and (+/-)-terbutaline was 0.128, 0.254, and 0.250, respectively. In contrast, Fh of (+)-terbutaline, (-)-terbutaline, and (+/-)-terbutaline was 0.979, 0.971, and 0.946, respectively. Fg and Fh of ethynylestradiol were 0.536 and 0.780, respectively. Simultaneous analysis also gave similar results, although the sequential analysis overestimated the intestinal availability. These results indicate that intestinal sulfation metabolism has more impact on intestinal availability than on hepatic availability, resulting in low bioavailability in humans.