To investigate airway physiology by use of inhaled aerosols, it is frequently necessary to measure the actual amount of material deposited on the airway wall as well as the site of particle deposition. To satisfy these needs, radiolabeled aerosols and gamma camera techniques have been used to measure regional deposition of inhaled particles. To make quantitative measurements of the amount deposited, previous investigators have used a "phantom" technique to indirectly calibrate the gamma camera for the attenuation of gamma rays through the lungs and chest wall. For this calibration, the phantom is a simulated lung containing a known amount of radioactivity. Radioactive counts emitted from the phantom are assumed to be attenuated in the same manner as the intact human lung. The present article describes a technique to determine directly the amount of inhaled aerosol deposited in the lung and simultaneously to calibrate the gamma camera for each individual subject. We used right angle light scattering and a gamma camera to measure individual values of the deposition fraction (DF) of inhaled aerosol deposited in the lung and the coefficient of attenuation (AC) of gamma rays in normal and obstructed lungs of human subjects. Radiolabeled monodisperse aerosols 1 and 2 microns in diameter were used. Knowledge of the activity of the inhaled aerosol (microcurie per liter), the volume inhaled, and the measured DF determined each subject's AC (counts per minute per microcurie). DF varied by an order of magnitude in normal (0.04 to 0.48) and obstructed (0.16 to 0.75) of subjects.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
-Methyldopa was intraarterially and orally administered to dogs at two dose levels in a randomized complete crossover design. The appearance of secondary peaks in the plasma concentration-time profiles indicated the presence of enterohepatically recycled methyldopa. This was established by the absence of a secondary peak following readministration of a dose after biliary cannulation and the detection of methyldopa in the bile of a cannulated dog. Enterohepatic recirculation was estimated to account for a mean of 16.2% of the area under the plasma concentration—time profile after intraarterial administration. Total systemic clearance, defined as the sum of elimination by all routes from the general circulation of the administered dose, and corrected for enterohepatic recirculation, averaged (±SD) 99.4 ±24.6 ml/min in the dog. An extended average apparent terminal half-life of 6.0±5.2hr was exhibited after oral administration compared to an average half-life of 3.1 ±1.8 hr following intraarterial administration. Elimination kinetics were linear in the dose range studied. Oral plasma concentration data suggest that the apparent bioavailable fraction may be dose dependent. 相似文献
Two Mannich-base prodrugs of 5-iodo-2-deoxycytidine (5-IDC) have been synthesized. The prodrugs exhibit increased lipid solubility compared to 5-IDC and rapidly revert to 5-IDC in buffer. One of the prodrugs delivered about twice as much 5-IDC from isopropyl myristate (IPM) through hairless mouse skin in diffusion-cell experiments as did 5-IDC from IPM. Subsequent applications of theophylline/ propylene glycol onto the diffusion cells to determine the effect of prodrug/IPM, 5-IDC/IPM, or IPM on the resistance of the skins to subsequent applications showed that the prodrug/IPM had no more effect than IPM itself. 相似文献
The vascular-extravascular exchange of fluid and solute molecules in a tissue is determined by three transport parameters (vascular permeability, P, hydraulic conductivity, Lp, and reflection coefficient, ); the surface area for exchange, A; and the transluminal concentration and pressure gradients. The transport parameters and the exchange area for a given molecule are governed by the structure of the vessel wall. In general, tumor vessels have wide interendothelial junctions; large number of fenestrae and transendothelial channels formed by vesicles; and discontinuous or absent basement membrane. While these factors favor movement of molecules across tumor vessels, high interstitial pressure and low microvascular pressure may retard extravasation of molecules and cells, especially in large tumors. These characteristics of the transvascular transport have significant implications in tumor growth, metastasis, detection and treatment. 相似文献
The lipophilicity of propranolol is increased by some bile salts which form ion-pairs. In the presence of taurodeoxycholate, the logarithm of the apparent partition coefficient (log P) of propranolol is increased. Moreover, the apparent diffusion constants in vitro of propranolol as ion-pairs at pH 3.0–6.0 are about 5–6 times higher than those of propranolol alone.
The area under the curve values of plasma concentration—time profiles of propranolol, following its oral administration to rabbits together with taurodeoxycholate, are about 1.4 times higher than those after administration of propranolol alone. Moreover, after the admistration of propranolol with taurodeoxycholate the plasma concentration rises more rapidly, with a point of inflection between 0.5 and 1.5 h, than after administration of propranolol alone.
Taurodeoxycholate does not modify the first-pass effect of propranolol in rabbits following intravenous and intraportal administration. The absorption of an oral dose of propranolol in the presence of taurodeoxycholate increases from 70% to 100%, due to the higher lipophilicity of the ion-pair. The plasma concentration—time curves suggest the hypothesis that greater absorption of the ion-pair occurs mainly in the upper region of the gastrointestinal tract. 相似文献
Equations have been developed that relate the concentration (or a parameter directly proportional to concentration, such as optical absorbance) of a weakly ionizable solute in a water-immiscible phase, in equilibrium with an aqueous phase, to the pH of the aqueous phase, the partition coefficient of the unionized solute and the phase volume ratio. These relationships have been used in the design of experimental methods for determining partition coefficients, which require measurement of solute concentration in only one phase. Data obtained in this way permit ready recognition of deviations from assumptions made in the development of the model; these assumptions include insolubility of the ionized solute in the water-immiscible phase and lack of interaction between buffer components and solute. Conditions for optimal liquid—liquid extraction of weakly ionizable solutes are more easily recognized. With these techniques, the negative logarithm of the acid dissociation constant (pK′a) and the logarithm of the octanol—water partition coefficient (log P) have been measured for warfarin (pK′a = 5.15 ± 0.04; log P = 2.82 ± 0.06), strychnine (pK′a = 8.29 ± 0.02; log P = 2.23 ± 0.04), phenol (pK′a = 9.88 ± 0.02; log P = 1.75 ± 0.05), procaine (pK′a = 8.11 ± 0.04; log P = 1.10 ± 0.08), and ephedrine (pK′a = 9.92 ± 0.01; log P = 1.65 ± 0.04) at 21°C. 相似文献