Publications

It is uncertain if respiratory heat loss or respiratory water loss is the stimulus for bronchoconstriction induced by isocapnic hyperpnea or exercise with dry air in subjects with asthma. We partially separated these 2 stimuli by having 18 subjects with asthma breathe dry air (0 mg/L water content) at increasing ventilations by isocapnic hyperpnea while we measured the increase in specific airway resistance (SRaw). The study was divided into 2 phases. In Phase 1, we used an apparatus with a single respiratory valve and evaluated the subjects' responses at 3 different inspired temperatures (-8.4, 20.5, and 39.4 degrees C). Seven of the subjects had esophageal catheters with 2 thermocouples in place to measure retrocardiac and retrotracheal temperatures. In this phase, we found that there were no significant differences in the ventilation required to cause a 100% increase in SRaw among the 3 different inspired temperatures (48.4 L/min, cold; 47.5 L/min, room temperature; 44.2 L/min, hot), even though the retrotracheal temperature fell more when the subjects breathed cold air at 40 L/min (2.1 degrees C) than when they breathed hot air (1.2 degrees C), suggesting greater airway cooling with the cold air. In Phase 2, in order to accurately measure inspired and exhaled temperatures and exhaled water content, we used 2 separate systems for delivering the inspired air and collecting the exhaled air at 2 different inspired temperatures (-21.4 and 38.9 degrees C). Again, we found that there was no significant difference in the ventilation required to cause a 100% increase in SRaw between the 2 different inspired temperatures (28.3 L/min, cold; 33.6 L/min, hot). When the subjects inhaled cold air, exhaled temperature was warmer than previously reported.(ABSTRACT TRUNCATED AT 250 WORDS)

The population pharmacokinetics of racemic warfarin was evaluated using 613 measured warfarin plasma concentrations from 32 adult hospitalized patients and 131 adult outpatients. Warfarin concentrations were measured in duplicate using a high-performance liquid chromatographic procedure. The pharmacokinetic model used was a one-compartment open model with first-order absorption (absorption rate constant set equal to 47 day-1) and first-order elimination. The extent of availability was assumed to be one. A linear regression model was used to evaluate the influence of various demographic factors on warfarin oral clearance. Age appeared to be an important determinant of warfarin clearance in this adult population. There was about a 1%/year decrease in oral clearance over the age range of 20-70 years. Smoking appeared to result in a 10% increase in warfarin clearance, while coadministration of the inducers phenytoin or phenobarbital yielded about a 30% increase in clearance. This study has yielded a predictive model that, when combined with appropriate pharmacological response data, may be useful in the design and adjustment of warfarin regimens.