The art and science of risk management: a US research-based industry perspective.

The research-based pharmaceutical industry in the US strongly supports the concepts of risk management and sees formal risk management as playing a major role in the development of safe medicines for the public, as well as providing a mechanism to ensure that decisions concerning individual drug benefit and risk are made based on scientific evidence. Safe medicines refer to those drugs whose benefits have been found to outweigh their risks when they are used according to the approved labelling. Risk management is the comprehensive and proactive application of scientifically based methodologies to identify, assess, communicate and minimise risk throughout the life cycle of a drug so as to establish and maintain a favourable benefit-risk balance in patients.

Monitoring outcomes of pregnancy following drug exposure: a company-based pregnancy registry program.

Women who discover they are pregnant after exposure to a drug and pregnant women who have a condition that requires continued treatment during pregnancy are told to balance the benefits and risks of the exposure to justify continuation of treatment, discontinuation of treatment or, possibly, pregnancy termination. However, there are limited data available to inform decision-making. The Merck Pregnancy Registry Program is a company-run pregnancy registry whose objective is to acquire and analyse information on drug exposures and pregnancy outcomes to better describe the safety profile of Merck products used during pregnancy.

Gastric antisecretory 9H-xanthen-9-amines.

A series of 9H-xanthen-9-amines possessing a wide variety of nitrogen substituents at C-9 was prepared for evaluation of gastric antisecretory activity. These substituents included the acetamidine, imidate, pyrimidine, thiazoline, quinuclidine, 2-hydrazinopyridine, aminopiperidine, aminoalkylimidazole, and aminoalkylpyridine moieties. The majority of compounds in this series inhibited gastric acid secretion when tested orally in the pylorus-ligated rat.

Regulation of the synthesis and release of slow-reacting substance of anaphylaxis from sensitized monkey lung.

Immunological challenge of sensitized fragmented cynomolgus monkey lung with anti-human IgE (immunoglobulin E) induced the appearance of slow reacting substance of anaphylaxis (SRS-A) in the tissue and evoked the release of SRS-A into the Tyrode's supernatant. The elevation of tissue or residual SRS-A levels was maximal 2 min after anti-IgE challenge and remained at that plateau for at least 60 min. The released SRS-A, first detectable 3 to 5 min after challenge, achieved a plateau by 10 min.

Immunologic histamine release in vitro from the heart and lung of the cynomolgus monkey.

Immunologic histamine release was evoked from the sensitized fragmented cardiac and pulmonary tissue of the cynomolgus monkey by a reverse anaphylactic reaction. Ventricular and pulmonary tissue released a similar fraction (approximately 6%) of the total tissue histamine when challenged with antihuman IgE, presumably reflecting the 'active' sensitization of the monkey in vivo. Passive sensitization of these tissues in vitro resulted in significantly greater immunologic histamine release in 6 of the 14 ventricles and d a similar fraction (approximately 6%) of the total tissue histamine when challenged with antihuman IgE, presumably reflecting the 'active' sensitization of the monkey in vivo.