The objective of this study was to develop an in vitro method to investigate the effect of ultrasound on the in vitro absorption of ibuprofen from a propylene glycol/water vehicle through human epidermis. A diffusion cell was modified so ultrasound could be applied to the vehicle and skin. Since ultrasound can increase the temperature underneath the area of application, control representing temperature effects ran concurrently to the ultrasound experiment. The results demonstrate that ultrasound can increase the penetration of ibuprofen through human skin. This increase in diffusion was greater than for controls where an equivalent increase in temperature was utilized. The results also indicate that evaporation of vehicle components may alter the skin/vehicle partition coefficient, decreasing the effects of ultrasound on the penetration of ibuprofen through the skin.

The influence of dietary protein levels on theophylline kinetics was examined in male Fischer 344 virgin rats of 2, 14 and 20 months of age fed for four weeks on a 23% (control) or 5% (low) protein diet ad libitum. Protein deficiency led to a significant decrease in body weight gain for the 2 month old rats (10.9% versus 26.5%). In addition, decreases in total body weight of 7.5% and 15.3% were seen for the 14 and 20 month old rats, respectively, on a low protein diet. Total proteins and albumin levels in plasma were not significantly affected by age or dietary protein levels. After intravenous administration of 10 mg/kg aminophylline, the average mean residence time (MRT) was significantly longer in 20 month old rats as compared to the younger rats, while 14 month old rats had a greater elimination rate constant than the 2 and 20 month old rats. There were significant reductions in the mean steady-state apparent volume of distribution (Vss) in the 2 and 14 month old rats on a low protein diet of 31% and 18%, respectively, while there was no difference between the diets in 20 month old rats. In addition, the Vss decreased from 0.71 L/kg to 0.57 L/kg in the 2 and 20 month old rats, respectively, on a normal protein diet. Dietary protein deficiency led to a significant reduction of total body clearance from approximately 73 to 45 ml/hr/kg in the 2 and 14 month old rats.2+p