Bruce E. Rodda

Hypotonic colon examination with glucagon.

In a clinical double-blind crossover study, the effects on barium enema examinations of intramuscular injections of a placebo, glucagon, atropine sulfate, and glucagon plus atropine sulfate were compared in 12 male volunteers for a total of 48 studies. With either atropine sulfate or glucagon there were decreased colon tonicity and increased comfort during the examination. Number and intensity of side effects were less with either placebo or glucagon than with atropine sulfate alone or combined with glucagon. The subject is more comfortable, the colon and small bowel more relaxed, intracolonic pressure less, and the examination more quickly completed after glucagon than after placebo or atropine sulfate.

Hypotonic Duodenography with Glucagon

In a double blind crossover study, the effects of 2 mg glucagon and 1 mg atropine sulfate on duodenal tonicity and motility were compared to placebo in 6 asymptomatic men. In a similar study, 2 mg glucagon and 30 mg propantheline bromide were compared to placebo. In 10 to 30 minutes after intramuscular administration of the drug there was a significant decrease in duodenal motility and tonicity with glucagon. Both tonicity and motility were near normal at 60 minutes. Responses to atropine sulfate and propantheline bromide were sometimes evident at 10, 30, and 60 minutes, but were variable and not consistently greater than with placebo. With atropine sulfate and propantheline bromide, intensity of reported side effects was greater than with placebo or glucagon.

Adsorption of Propoxyphene Hydrochloride by Activated Charcoal

(1972). Adsorption of Propoxyphene Hydrochloride by Activated Charcoal. Clinical Toxicology: Vol. 5, No. 3, pp. 317-329.

Problems associated with bioavailability and dosage regimen studies in man

The problems associated with bioavailability studies begin with the initial request for information. Clinical pharmacology testing units are ultimately responsible both for evaluating internally and externally generated requests and for implementing studies regardless of their motivations (scientific, regulatory, or marketing). Once the inquiry is made, the clinical staff becomes concerned with judgments of risk vs. benefit and with experimental design. Each protocol must pass peer evaluation both for scientific validity and for ethical standards of human experimentation. Initially in our unit, the protocol is evaluated by a committee whose members represent medicine, basic science, and statistics. This group not only considers the ethics but also stresses scientific and, more recently, regulatory matters. Final approval is granted by a review committee dissociated from the unit and constituted as outlined in the Federal Register (1). This committee includes, in addition to scientific representatives, members of the legal profession and the clergy. The study objective (see Table I) is the prime consideration of protocol design. Careful examination of the goals may help one define potential benefits and hence may serve in the benefit-risk judgments. In reviewing this list, the difficulty in achieving the goals appears to increase in the order presented. The last item, bioavailability-pharmacological activity correlations, has rarely been demonstrated clearly.

Cholecystography: A Cost Reduction Study

A total of 450 roentgenograms of 45 patients were analyzed to see whether a minimum number of procedures could be established for diagnostic cholecystography. Films were taken before and after a fatty meal, after viewing pictures of food, and in the upright, prone, and decubitus positions. There was no psychogenic effect on gallbladder contraction. In 51% of patients the 20-minute post-fat decubitus film was the most diagnostic. The 20-minute post-fat postero-antcrior film was most diagnostic in 29%, and the combination of the two was overwhelmingly diagnostic in 80%. The combination of these two films with a single pre-fat film produced a scientifically valid cost improvement without decreased diagnostic accuracy.

A pharmacokinetic method for designing prolonged-release formulations—Propoxyphene hydrochloride

Many prolonged-release preparations are designed so that a certain fraction is immediately available for absorption upon administration, while the remainder becomes available for absorption at an effectively constant rate. Recently, a number of prolonged-release propoxyphene hydrochloride formulations have been designed to dissolve in this manner in vitro.We employed a pharmacokinetic model, product dissolution data, and historical plasma concentration data to predict the plasma propoxyphene concentrations which might result from a particular mix and thus minimize the number of formulations requiring evaluation in subjects.