Interpretation and application of world-wide safety data on diltiazem.

The safety of medicinal agents being introduced into the marketplace is of growing concern to consumers, health care providers, and regulatory agencies. Although there are ever increasing efforts to improve techniques for testing drugs, and for anticipating and confirming possible adverse effects, arrangements for monitoring and detecting adverse drug reactions are far from satisfactory. Some factors which need to be understood in order to appropriately interpret data include: maturation processes; pretesting affects, measuring instruments affects; selection bias; and the affects of differential experimental mortality. A safety profile has been presented for the calcium entry blocker diltiazem hydrochloride. Efforts were made to focus attention upon the source of safety information as it relates to the quality of the report. The data presented suggests that diltiazem hydrochloride has a low incidence of adverse experiences.

Clinical experience with diltiazem in Japan.

In a cooperative postmarketing study, 3,913 Japanese patients received diltiazem, an orally administered calcium channel blocking agent, for 30 to over 360 days. Drug safety was assessed by monthly evaluations of subjective symptoms, electrocardiographic recordings, adverse experiences, vital signs, and biochemical profiles. Original case report forms were processed and analyzed in the United States. None of the observed adverse experiences were serious or life threatening. They occurred in 1.8% of the patients and primarily involved the gastrointestinal system; anorexia and nausea were the most common adverse effects. The majority of the other adverse experiences were extensions of the drug's pharmacologic effects. Diltiazem appears to cause relatively minor clinical toxicity at a low frequency.

In vitro and In vivo evaluations of a tableted antacid and sucralfate, a new antiulcer agent.

Sucralfate is a nonsystemic drug used in the therapy of peptic ulcer disease. It is an aluminum salt of a sulfated disaccharide which adheres to ulcerated sites and forms a cytoprotective barrier to acid peptic digestion. The purposes of this study were to determine whether sucralfate had antacid activity in humans and to test the validity of the in vitro antacid qualifying test by comparing its results for tableted products with those of in vivo studies. In the in vitro antacid qualifying test Maalox #1 (4 tablets) passes and sucralfate (1 gm.) failed. These findings were consistent with the results of in vivo tests utilizing a telemetric device, the Heidelberg capsule and tube aspirations. We conclude that sucralfate does not possess antacid properties and that the results of the standard in vitro antacid qualifying test correlated well with those of in vitro studies.

Variability of exercise performance during long-term placebo treatment.

Although exercise testing is commonly used to determine the efficacy of antianginal drugs, there is little information on the effect of frequent exposure to such testing over periods of long as 6 mo. In or study 10 patients (four men and six women) with stable angina pectoris received placebo for 6 mo. Treadmill testing followed a modified Bruce protocol. All patients exercised to an end point of typical anginal pain and 1 mm or more of ST depression. The first treadmill test for diagnostic purposes was followed by testing every 2 wk for 6 mo. Sublingual nitroglycerin was permitted to abort attacks of angina. Parameters evaluated included heart rate, double product, and duration of exercise. There was no change in the maximal heart rate (mean = 109 at 2 wk and 112 at 6 mo) or double product (mean = 17,002 at 2 wk and 17,249 at 6 mo). On the other hand, duration increased (mean 7.8 min at two wk and 9.9 min at 6 mo). Thus, although treadmill testing showed reproducible measurements of maximal heart rate and double product over 6 mo, exercise duration increased progressively.

Does basic aluminum sucrose sulfate affect blood coagulability?

Basic aluminum sucrose sulfate (sucralfate) is a sulfated disaccharide similar in structure to heparin that has been shown not to possess anticoagulant effects in vitro or in animal models. As an adjunct to a study of the efficacy of sucralfate in the treatment of duodenal ulcer disease, we evaluated the drug's anticoagulant effects. Twenty-eight patients were randimized to treatment with sucralfate. Evaluations of prothrombin time and activated partial thromboplastin time, prestudy and after two and/or four weeks of treatment with sucralfate, demonstrated no evidence of anticoagulant activity.

Methods for increasing bioavailability of cycloplegics.

Since it has been shown that (1) fluid instilled in the pouch created by pulling the lower lid away from the eyeball is entrapped, (2) no fluids move into the lacrimal sac when the eyelids are shut and (3) gravity is important in tear-flow dynamics, we reasoned that an instillation technique for topical ocular drugs could be devised which would increase the drug effect for a given amount of drug. To test this hypothesis we administered one drop of 0.5% tropicamide to the right eyes of 12 young adults using an experimental method of instillation and to the left eyes using the conventional technique. The experimental technique produced a significantly greater loss of accommodation than the conventional technique. Wtih this experimental or similar technique, it may be possible to use lower concentrations of a drug to produce the same ocular effects produced by a higher concentration instilled in the conventional manner.