Relative affinity of 17 alpha- and/or 21-esters and 17 alpha, 21-diesters of cortisol for a glucocorticoid receptor from rat thymocytes.

The affinity, relative to cortisol (1), of 17 alpha- and 21-esters and 17 alpha,21-diesters of cortisol for the glucocorticoid receptor of rat thymus cytosol was determined by a competitive binding assay which used [3H]dexamethasone. Esterification of the 21-hydroxy group of cortisol caused a loss of relative affinity to 0.046 for acetate and 0.32 for valerate. Esterification of the 17 alpha-hydroxy group resulted in an increase in relative affinity to 1.14 for acetate, 12.4 for butyrate, and 11.5 for valerate. Diesters had relative affinities which reflected both trends. Thus, the 21-acetate, 21-propionate, 21-butyrate, and 21-valerate of cortisol 17-acetate had relative affinities of 0.036, 0.093, 0.152, and 0.272. The 21-acetate, 21-propionate, and 21-butyrate of cortisol 17-valerate had relative affinities of 0.76, 1.17, and 1.33.

Theophylline bioavailability in the dog.

The bioavailability of theophylline following single oral doses of a theophylline capsule, a theophylline tablet, and an aminophylline tablet in beagle dogs was compared against an intravenous standard. Plasma theophylline levels after oral and intravenous drug administration were described by the one-compartment open model. The onset of theophylline absorption from the oral products was rapid. While the theophylline tablet showed a slower absorption rate than the capsule or the aminophylline tablet, all three products appeared to be completely bioavailable.

Effect of caffeine on circulating theophylline levels in beagle dogs.

The pharmacokinetic interactions of caffeine with theophylline were examined in two beagle dogs by administering 100 mg of aminophylline intravenously, 3 weeks before and immediately after repeated oral doses of caffeine. Serial plasma samples were analyzed for caffeine and theophylline simultaneously by high-performance liquid chromatography. Upon multiple oral dosing, 100 mg every 12 hr for 7 days, the caffeine half-life increased slightly in one dog but decreased in the other. As predicted from single-dose data, caffeine accumulation in plasma after repeated doses was slight, while plasma levels of the N-demethylated metabolite, theophylline, rose to about three times the initial values. After rapid intravenous doses of aminophylline, the theophylline half-life was 5-7 hr, which decreased slightly when the drug was administered concomitantly with caffeine during steady state of caffeine. The theophylline volume of distribution (0.75 liter/kg) was unaffected by caffeine. On the other hand, an acute aminophylline injection prolonged the elimination half-life and increased the apparent volume of distribution of caffeine, causing little overall change in its plasma clearance. The results suggested that interactions between theophylline and caffeine may be attributed to changes in drug distribution and drug elimination characteristics.