A new approach is proposed for conducting pharmacokinetic studies of a pharmacologically active botanical extract containing mixtures of several classes of active and inactive compounds. We are currently developing the botanical extract as a botanical drug under an allowed Investigational New Drug (IND) by the FDA. We have identified key marker compounds for PK studies based on relevant biological activity and relative abundance in the extract. We propose to develop and validate a sensitive and accurate analytical method for quantitation of the marker compounds from plasma matrix in Phase I. Development of these methods will ultimately generate a robust approach for conducting routine GLP PK studies in animals and humans, which will be the subject of Phase II. The PK studies in human will provide new information, which will be used for NDA approval of the botanical drug as an effective treatment of insomnia, a condition with a large unmet medical need for effective and safe therapeutics with a low adverse effect profile. Successful completion of the long-range goals also will enable development of unique formulations and selection of dose regimen in elderly populations. PROPOSED COMMERCIAL APPLICATION: This project will support the development, under IND, of an important new class of drugs, the Botanical Drug Product. The botanical extract, which is the subject of this study, will be developed as an effective and safe new therapeutic for insomnia, a condition where currently 95% of those affected by the disease are not currently taking prescription medication. The botanical extract we will develop as a new drug has a favorable profile relative to the "ideal" drug for treatment of this condition
