Drug discovery bioavailability

However, most natural peptides are composed of L-form a-amino acids and because of the ubiquitous prevalence of peptidases they have limited biostability, and consequently low bioavailability. Thus, a novel field of peptidomimetics has emerged in drug discovery, in attempts to design non-peptide compounds mimicking the pharmacophore and thus the activity of the original peptide. 

The last step of the drug discovery process involves the testing of lead compounds to address issues such as efficacy, bioavailability, and safety. Testing may include in vitro assays but ultimately would require a suitable disease model and studies in animals. Many compounds may need to be designed and synthesized to identify the one compound with all the desired properties. Such a compound can be advanced to preclinical studies and eventually to the clinic. 

This chapter will review some of the important methods for carrying out in vivo absorption and bioavailability studies, as well as attempt to provide an overview of how the information may be used in the drug discovery process. The chapter is aimed at medicinal chemists and thus will focus on the use of animals in discovery phase absorption, distribution, metabolism, and excretion/pharmacokinetic (ADME/PK) studies, rather than the design of studies that are for regulatory submission, or part of a development safety package. 

A model for predicting oral bioavailability is an important tool, both in the early phases of drug discovery to select the most promising leads for further optimization, and in the later stages to select candidates for clinical development. The... 

As part of new drug discovery, the trend toward screening for metabolites in plasma samples being assayed for the dosed compound (NCE) is increasing. This effort is sometimes called metabolite profiling116 and it is important for two reasons (1) for compounds with low bioavailability due to extensive metabolism, metabolites may help medicinal chemists learn to modify the NCE to block... 

Identification of metabolic reactions at an early phase can significantly affect the drug discovery process, because bioavailability, activity, toxicity, distribution and final elimination all depend on metabolic biotransformations [1], Once obtained, this information can help researchers judge whether or not a potential candidate should be eliminated from the pipeline or modified to reduce the affinity for CYP antitarget enzymes. 

The present revised textbook on Pharmaceutical Drug Analysis caters for the much needed handbook and reference book, which is absolutely current with regard to the esteemed philosophy of analytical chemistry, an obvious solid support towards drug discovery, development, stability studies, bioavailability and pharmacokinetic studies, and above all the quality assurance of pure drugs together with their respective dosage forms. 

Stoner CL, Cleton A, Johnson K, Oh D-M, Hallak H, Brodfuehrer J, Surendran N, Han H-K (2004) Integrated oral bioavailability projection using in vitro screening data as a selection tool in drug discovery. Int. J. Pharm. 269 241-249. 

A variety of in vitro assays are available to assess important parameters that impact bioavailability and these pharmaceutical profiling assays are commonly run to support drug discovery efforts. The major challenge is the interpretation of these results. Misinterpretation can lead to dropping promising compounds or alternatively taking... 

Oral bioavailability is one of principal pharmacokinetic properties in drug discovery. It represents the percentage of an oral dose that is available to produce pharmacological actions, in other words, the fraction of the oral dose that reaches the system circulation in an active form. By the definition, when a drug is administered intravenously, its bioavailability is 100%. However, when a medication is administered via other routes, especially orally, its bioavailability decreases due to incomplete absorption and first-pass metabolism. 

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