Evaluation of orally administered activated charcoal on intestinal dialysis of intravenously administered M79175, an aldose reductase inhibitor, in rats.

The effect of oral administration of activated charcoal on serum elimination of 14C-M79175 injected intravenously in rats was studied. In situ single-pass perfusion studies showed that M79175 and/or its metabolites was transported into the small intestinal lumen. Total radioactivity expressed as equivalents of M79175 exsorbed in the perfusate and excreted in the bile juice was 3.2% and 2.0%, respectively, of dose. Oral administration of multiple doses of activated charcoal significantly decreased the serum concentration and serum half-life of 14C-M79175. The fecal excretion of 14C-M79175 after treatment with activated charcoal was increased when compared to that in the control. On the other hand, urinary excretion of 14C-M79175 after treatment with activated charcoal was decreased. However, there was no significant difference in the cumulative amounts of total excretion (fecal plus urinary excretion) between rats with activated charcoal treatment and rats without charcoal treatment. These results suggest that intestinal dialysis by oral activated charcoal is a reasonable method to enhance the elimination of M79175 from the serum in case of overdose of the drug.

Study of bioavailability and pharmacokinetics of theophylline following administration of two sustained release dosage forms as assessed by salivary data: Part II.

Bioavailability and pharmacokinetics of theophylline following administration of a marketed sustained release tablet (Theo-Dur) and a newly designed sustained release tablet (E-0686) have been studied in fifteen healthy volunteers by measuring plasma and salivary concentrations. The theophylline level in saliva was 42.3 +/- 0.008 (s.e.m.) % of the plasma level and its correlation coefficient was 0.908. This observation suggests that salivary levels are considered to be a good indicator of the plasma concentration of theophylline. Interformulation variability in the saliva/plasma ratio was not significant in four occasions (p greater than 0.05). Thus, it was confirmed that the saliva/plasma ratio was nearly constant after administration of sustained release preparations of theophylline. Bioequivalency as to the extent of bioavailability of the two preparations was demonstrated by measurements of plasma and salivary levels. Compared to the theophylline levels in non-smokers, lower concentrations were observed in smokers at elimination phase by measurements of both the plasma and salivary levels, but shorter elimination half-life in smokers was indicated only in salivary data.

Effect of food on bioavailability and pharmacokinetics of theophylline following administration of two sustained release dosage forms: Part I.

Bioavailability and pharmacokinetics of theophylline following administration of a marketed sustained release tablet (Theo-Dur) and a newly designed sustained release tablet (E-0686) have been studied in fifteen healthy volunteers under overnight fasting and non-fasting conditions. Higher concentrations at early absorption phase under fasting conditions than under non-fasting conditions were observed after administration of Theo-Dur, whereas little difference in plasma concentrations was noted when E-0686 was administered under fasting and non-fasting conditions. Bioequivalency was demonstrated depending upon the extent of bioavailability of the two preparations. Compared to the theophylline levels in non-smokers, significantly lower concentrations at elimination phase and AUC0-infinity values were observed in smokers in each treatment (p less than 0.05). E-0686 exhibited almost the same rate constant in dissolution in vitro and in absorption in vivo, while Theo-Dur did not. Therefore, it may be concluded that E-0686 is a well-designed sustained release preparation that releases theophylline in vivo at a given rate which can be easily determined in vitro.

Sustained release of theophylline from hydroxypropylcellulose tablets.

Compressed tablets were prepared from theophylline and hydroxypropylcellulose. Effects of the viscosity grades of the polymer, the mixing ratios of two polymers with different viscosity grades, and the polymer contents in the tablets on release patterns of theophylline were examined in vitro. Release rate was decreased with increasing viscosity designation and polymer contents in the tablets. In salivary level profiles of theophylline following oral administration of sustained-release tablets to five human volunteers, a low but sustained level was noted indicating sustained release of the drug from the tablets in vivo.