Preclinical pharmacology of saralasin.

Saralasin is a highly soluble and stable AII antagonist with a relatively short half-life; therefore, its effects are rapidly reversible when administered i.v. Acute and subacute studies have shown only transient toxicosis with no significant pathology or teratology. Saralasin's angiotensin receptor affinity has been correlated with its biologic acitivity. Observations from the pharmacodynamic investigations have shown that saralasin is a specific competitive antagonist of the vascular, renal, adrenal, cardiac, and central nervous system actions of AII. In addition, these studies further support the utility of saralasin as a diagnostic and therapeutic agent for patients whose hypertension is due directly to AII.

Quality assurance operations: good clinical practices.

The pharmaceutical industry sponsor bears the ultimate responsibility for the verification of all clinical data submitted to the FDA in support of a New Drug Application (NDA). The author provides an overview of a systematic approach to providing quality assurance for all clinical data collected in the course of human trials with research compounds. This systemic approach includes such features as: Standard Operating Procedures Manuals, the development of a quality assurance function within the organization, detailed documentation for all monitoring activities, careful assessment of all clinical research data collected, and an emphasis on preventive measures that can be introduced to assure the quality of subsequent research data.

International regulatory aspects of clinical periodontal research.

The Food and Drug Administration (FDA) was the pioneer regulatory agency to set standards for clinical studies aimed at approval of new drugs. For years the FDA's rules represented the most thorough, stringent, and consistent policy. Now most other developed countries have comparable requirements for the conduct of clinical trials. The European Community (EC). Canadian, and Japanese regulations are most important for United States (US) scientists attempting to globalize their research. Regulations in Eastern Europe, some Asian countries, and Latin America are of growing importance. The Pacific-Rim appears to be the fastest growing pharmaceutical market in the next decade. Currently, the EC and Japan's Good Clinical Practice (GCP) regulations are more detailed than those of the US. Moreover, the World Health Organization recently published GCP recommendations similar to the EC requirements. Well-designed and well-controlled studies done in the EC, US, and other developed countries are generally accepted throughout the world. Japan and some other countries require studies in local patients. American scientists cannot expect to conduct studies in other countries as principal investigators, but many are associated with national clinicians. Mutual recognition of marketing approvals is the ultimate goal for the globalization of drug research. While it is the objective of the Scheme for the Mutual Recognition of Evaluation Reports on Pharmaceutical Products and the EC Decentralized Procedure, it is not apparent when the FDA will totally accept another regulatory body's approval decision. The International Conference on Harmonization involves the EC, Japan, and the US. This most important series of meetings will finally align the major countries more closely in regulating clinical studies and the production of safe, effective, and quality products, especially in these times of worldwide economic considerations and health care reform. It is imperative that US dental scientists become more familiar with pertinent regulations in leading foreign countries.

The antidiarrheal action of bismuth subsalicylate in the mouse and the rat.

The antidiarrheal effectiveness of bismuth subsalicylate was determined in two species of laboratory animals. Doses of castor oil were, at first, found to accelerate significantly the movement of a charcoal test meal along the small intestine of the mouse and rat and also to increase both the fecal output (dry or wet weight) and the frequency of diarrhea in mice. Bismuth subsalicylate significantly prevented the enhancement of charcoal-meal transport induced by castor oil in both mice and rats. Increased fecal outut (dry or wet weight) and increased frequency of diarrhea in mice were also significantly reduced by bismuth subsalicylate in a dose-related fashion. The findings in these experiments lead to the definitive conclusion that bismuth subsalicylate exerts antidiarrheal activity in the mouse and in the rat and support its use in therapy of common clinical diarrheal states.

Protective effect of Pepto-Bismol liquid on the gastric mucosa of rats.

Pepto-Bismol liquid (primary active constituent, bismuth subsalicy-late) protected the gastric mucosa of rats against the formation of hemorrhagic lesions or erosions in response to cold + restraint stress, to a combination of aspirin and cold + restraint stress, and to ethyl alcohol. The protective effect of Pepto-Bismol in these studies was clearly demonstrated. Although the mechanism of action of Pepto-Bismol was not delineated, there was a suggestion that the degree of coating of the gastric mucosa was related to protection.