The dose dependency of the pharmacokinetics of dexamethasone and its influence on the endogenous secretion of cortisol has been studied in healthy females. The maximum plasma level occurred between 1.6 and 2.0 h after doses of 0.5-3.0 mg independent of the type of administration. AUC, distribution volume, plasma clearance and cmax did not increase in proportion to the dose but only by the factor of about 0.6-0.7 after the oral administration of 0.5-1.5 mg. Comparatively high values were reached after 3.0 mg i.m. This may be due to reduced bioavailability of the oral doses. Within the first 12 h after the administration of 0.5-3.0 mg, endogenous cortisol secretion was influenced independent of dose. However, the suppressive effect after 24 h was dose dependent and amounted to approximately 24% for 0.5 mg p.o., 62% for 1.5 mg p.o. and 90% for 3.0 mg i.m. In the case of administration every second day, the integral reduction within 24 h after the administration of 0.5 mg dexamethasone was 44 to 65% and for 1.5 mg between 59 and 62%.

The absorption of a theophylline solution containing 80-120 mg doses delivered to different sites in the gastro-intestinal tract has been determined in 3 male volunteers using a remote controlled drug release system (HF-capsule). There was no difference between the stomach, ileum and the colon in the amount of theophylline absorbed (AUC). The T 1/2abs of theophylline absorbed via the colon was prolonged when compared with that entering via the upper gastro-intestinal tract. The results provide a rational basis for the further development of theophylline formulations and are indispensable for planned development and to account for variation in the bioavailability of retarded release drug preparations.

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This paper presents the results of animal tests and clinical studies on the metabolism of radioactive cyclophosphamide (Endoxan). The authors conclude that most of the metabolic breakdown of Endoxan occurs within the first two to three hours after administration. Further radiochromatographical investigations must be undertaken before the distribution of cytostatically active metabolites and their concentration in the tumor tissue can be elucidated. Studies on cerebral tumors have shown that the concentration is probably higher in the peripheral zones of the tumor than in the center.