Pharmacokinetic optimization in drug research

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In the current era of combinatorial chemistry and high-throughput technologies, thousands of bioactive compounds, known as hits, are identified. However, the journey from hits to lead compounds and ultimately to optimized clinical candidates is lengthy and fraught with challenges, particularly in screening, designing, and optimizing pharmacokinetic properties. This has become a significant bottleneck in drug research. To address the high attrition rates of compounds due to hidden pharmacokinetic issues, researchers are integrating structure-permeation, structure-distribution, structure-metabolism, and structure-toxicity relations into drug design. Advanced biological, physicochemical, and computational methods are being developed to enhance the clinical relevance of drug design and to swiftly eliminate compounds with poor properties. This comprehensive work features contributions from international experts, outlining modern strategies to optimize gastrointestinal absorption, protein binding, brain permeation, and metabolic profiles. Biological strategies include cell cultures and high-throughput screening, while physicochemical strategies focus on solubility, lipophilicity, and related molecular properties as predictors of pharmacokinetic behavior. The book also delves into computational strategies like virtual screening and molecular modeling. It offers insights into molecular properties from both biological and physicochemi