Pre-clinical

Medline covers primarily biomedical literature, containing more than 13 million citations (October, 2002) of articles from more than 4600 journals published since 1958 [18]. The database covers basic biomedical research, clinical sciences, dentistry, pharmacy, veterinary medicine, pre-clinical sciences, and life science. Medline, a subset of PubMed, is a bibliographic database produced by the US Nationcil Library of Medicine (NLM). The database is available free of charge via SciFinder Scholar or PubMed [19]. 

M867 Merck-Frosst Caspase-3 and -7 (reversible) Kj 1.4 nM (C-3) Kj 8.9 nM (C-7) Sepsis Pre-clinical... 

Hofland LJ, der Hoek J, van Feelders R et al (2005) Pre-clinical and clinical experiences with novel somatostatin ligands advantages, disadvantages and new prospects. J Endocrinol Invest 28(11 Suppl) 36-42... 

In infectious disease compounds such as ANA975 (phase I trials) and Resiquimod (phase II trails) have been developed to target Hepatitis C and genital herpes, respectively. DRS954 is a TLR-7 and 9 antagonist in pre-clinical trials for Systemic Lupus Erythematosus (SLE). 

Safety (S) relating to in-vitro and in-vivo pre-clinical studies. 

In summary, the characteristics of the drug and the disease or condition may suggest a likely route and mode of delivery. Considerable vork is required to develop and optimise an appropriate drug presentation. The suitability of any particular strategy must be verified by undertaking the extensive pharmacodynamic and pharmacokinetic studies that form part of the pre-clinical and clinical trials. 

The majority of non-clinical studies are undertaken in the pre-clinical phase of drug development. These studies serve both to guide the developer and satisfy the regulatory authorities. The objectives of this phase can be summarised as follows ... 

Safety and quality aspects are the main topics that must be addressed from a regulatory perspective at the pre-clinical phase of drug development. Indicative efficacy data will also be obtained, but authoritative data can be obtained only from clinical studies conducted with humans. Safety and preliminary efficacy indications... 

In addition to the safety studies, extensive investigations must be undertaken to establish the quality of the drug substance and product(s) during the pre-clinical phase. These will usually commence with drug discovery, where the initial characterisation of... 

Pharmacological Properties (pharmacodynamics, pharmacokinetics, pre-clinical safety data)... 

Clinical trials must be conducted to establish safety in each target animal species which, in the majority of cases, will include food-producing species. Although the same types of animal may be involved in both pre-clinical and clinical trials, dear distinctions can be drawn between each type of study. Pre-clinical studies are only conducted in animals that are kept for the purposes of laboratory research, and that are usually maintained in a very controlled environment. Clinical trials, on the other hand, are conducted in animals that are representative of the normal conditions (field conditions) and purposes for which they are maintained. 

The EU will accept applications without supporting pre-clinical and clinical data, if it can be demonstrated that the active substances have been in well-established medical use in the Community for at least 10 years, with recognised efficacy and an acceptable level of safety. This route would be appropriate for many common over-the-counter (OTC) products. Safety and efficacy is supported by providing copies of published scientific literature as part of the submission that is, the submission relies on safety and efficacy data available in the public domain, as opposed to confidential data from authorised applications that is the cornerstone of generic applications. 

Standard authorisation Yes (SPC) Yes (CMC and Stability) Yes (Pre-clinical and Clinical data) Yes (Clinical data)... 

All the nucleoside (and nucleotide) analogues that have entered the clinic for the treatment of HBV infections (i.e., nucleoside analogues lamivudine, entecavir, tel-bivudine nucleotide analogues adefovir and tenofovir) are fairly well tolerated without side effects that would preclude their long-term usage. The nucleoside analogues in (pre)clinical development for the treatment of HCV infections are not yet sufficiently advanced to assess their tolerability and/or safety. 

Kopf-Maier, P., Kopf H. Transition and Main-Group Metal Cyclopentadienyl Complexes Pre-clinical Studies on a Series of Antitumor Agents of Different Structural Type. Vol. 70, pp. 103-185. 

This article summarises the general characteristics of a novel antibacterial target, peptide deformylase (PDF) and reviews the design, structure-activity relationships (SAR) and properties of known PDF inhibitors, including pre-clinical and clinical data for the most advanced members of this class. 

Most recently, the Abbott group disclosed a series of benzofurans with potent affinity for the human and rat receptors. ABT-239 (29) is one of the more extensively profiled members of this series. (29) has a K of 0.45 nM at the human receptor [95], good rat pharmacokinetics and demonstrated efficacy in models of cognition [96]. Recently, a scaleable synthesis of ABT-239 has been reported [97] and the researchers have published detailed accounts on the pre-clinical pharmacokinetics and efficacy of this compound [98, 99], indicating continued interest in this series of H3 antagonists. 

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