Efficacy of inhaled fluticasone propionate in asthma results from topical and not from systemic activity.

The objective of this study was to determine whether the therapeutic benefits of inhaled fluticasone propionate are mediated through topical or systemic effects. Two hundred seventy-four patients with asthma receiving beclomethasone dipropionate or triamcinolone acetonide during a 2-wk, single-blind, run-in period were randomized to inhaled fluticasone propionate powder 100 or 500 micrograms twice daily, oral fluticasone propionate 20 mg once daily, or placebo during a 6-wk treatment period. Patients receiving inhaled fluticasone propionate had a significantly greater probability of remaining in the study over time compared with patients receiving oral fluticasone propionate or placebo (p = 0.001). FEV1 and PEF rates at end point were significantly higher with inhaled fluticasone propionate treatment regimens than with oral fluticasone propionate (with the exception of PEF rates for inhaled fluticasone propionate 100 micrograms) or placebo treatments (p < or = 0.004). Systemic exposure to fluticasone propionate as assessed by trough plasma concentrations and/or 12-hr plasma concentration area under the curve analyses (AUC12) was higher with the oral fluticasone propionate than with the two inhaled fluticasone propionate treatment groups. The results of this study suggest that the therapeutic benefits of inhaled fluticasone propionate are mediated through topical effects in the lungs and not through systemic effects.

Plant antitumor agents, 19. Novel triterpenes from Maprounea africana.

Four new pentacyclic triterpenes have been isolated from Maprounea africana. These triterpenes are members of the previously unknown urs-12-en-29-oic acid series. The structures of these compounds were deduced from spectral and chemical evidence. The parent compound, maprounic acid, was identified as 3B-hydroxyurs-12-en-29-oic acid. The remaining three triterpenes were identified as maprounic acid 3-p-hydroxybenzoate, 7 beta-hydroxymaprounic acid 3-p-hydroxybenzoate, and 2 alpha-hydroxymaprounic acid 2,3-bis-p-hydroxybenzoate. Of the four triterpenes, only the 7 beta-hydroxy derivative exhibited in vivo P-388 activity.

The pharmacist's role as a member of the institutional review board.

Since World War II, concern about the protection of human subjects in biomedical research has increased considerably. The Nuremberg Code and the Helsinki Declaration have been published. The United States Department of Health, Education, and Welfare (DHEW) has developed and published regulations that specify a review process which research institutions must follow in order to receive DHEW funds for research involving human subjects. Part of this process includes a review of research projects by an Institutional Review Board (IRB). Membership on the IRB must be varied and should include allied scientists. Because many of the projects include investigational drugs, the inclusion of a pharmacist as a member is logical. The pharmacist, if properly selected and prepared, can play a vital role in the review of research projects by assisting in the evaluation of the scientific merit of the plan, the appropriateness of the volunteer agreement, and the regulatory compliance of the project. The selected pharmacist should view the duty as another opportunity to practice clinical pharmacy.

Isolation and structural studies of coprine, the disulfiram-like constituent of Coprinus atramentarius.

Coprine, the constituent of the mushroom Coprinus atramentarius Fr. responsible for its disulfiram-like activity, was isolated. Chemical and spectral data indicate that the compound is N5-(1-hydroxycyclopropyl)glutamine. Although coprine was shown to produce hyperaldehydemia in mice following ethanol ingestion, the compound was not found to be an inhibitor of mouse liver aldehyde dehydrogenase in vitro.