Disposition of bupropion in healthy volunteers and subjects with alcoholic liver disease.

Bupropion hydrochloride is a new monocyclic antidepressant. In humans, its disposition results in the formation of three major metabolites: the morpholinol metabolite, the erythroamino alcohol, and the threoamino alcohol metabolite. Bupropion's disposition was monitored following a single oral 200 mg dose in eight healthy volunteers and eight age- (44.5 +/- 8.4 years) and weight- (77.4 +/- 6.7 kg) matched volunteers with alcoholic liver disease. This latter group is of interest because the incidence of depression is more frequent in alcoholics than in the general population, and the liver is the major route of elimination for cyclic antidepressants. The mean elimination half-life of the morpholinol metabolite was significantly prolonged in subjects with alcoholic liver disease (32.2 +/- 13.5 vs. 21.1 +/- 4.9 hours (p less than 0.05), while the differences in bupropion (17.3 +/- 8.6 hours vs. 16.5 +/- 10.4 hours for healthy subjects and subjects with alcoholic liver disease, respectively), erythroamino alcohol (26.1 +/- 13.3 hours vs. 29.8 +/- 6.9 hours for healthy subjects and subjects with alcoholic liver disease, respectively), and threoamino alcohol (25.5 +/- 8.6 hours vs. 23.4 +/- 10.7 hours for healthy subjects and subjects with alcoholic liver disease, respectively) were minimal. Mean area under the plasma concentration time curves for bupropion and metabolites were increased in subjects with alcoholic liver disease; however, clear differences between means of these small groups did not emerge, probably due to the increased variability of bupropion pharmacokinetics in these subjects. As a therapeutic agent for the treatment of depression in chronic alcoholics who may consume alcohol in combination with their antidepressant therapy, the lack of sedation with bupropion could be advantageous.(ABSTRACT TRUNCATED AT 250 WORDS)

Inadequacy of FDA dosing guidelines for intravenous theophylline.

The ability of a dosing regimen of intravenous theophylline to achieve therapeutic serum theophylline concentrations was evaluated. Intravenous theophylline was administered to 25 adult patients with acute bronchospasm using dosing guidelines 20 percent higher than FDA recommendations. The dose of theophylline was determined by assignment to one of four clinical categories. Blood samples for determination of serum theophylline concentrations were collected 12 and 24 hours after initiation of a constant infusion. Differences between mean observed and target theophylline concentrations did not achieve statistical significance. All patients in categories 1 and 2 achieved therapeutic concentrations of theophylline. Most of those with subtherapeutic levels were smokers suffering from multiple diseases. We conclude that current FDA recommendations for dosing intravenous theophylline are unreliable for routine use in category 3 and 4 patients. Further work is necessary to evaluate these recommendations in pediatric and category 1 and 2 patients.