Drug design pharmacokinetics

Smith, D. A., Van de Waterbeemd, H., Walker, D. K. Pharmacokinetics and Metabolism in Drug Design, 2nd edn. Methods and Principles in Medicinal Chemistry), Wiley-VCH, Weinheim, 2006. 

Kubinyi, H., Hydrogen bonding The last mystery in drug design in Testa, B. van de Waterbeemd, H. Folkers, G. Guy, R. (eds.), Pharmacokinetic Optimization in Drug Research, Verlag Helvetica Chimica Acta, Zurich and Wiley-VCH, Weinheim, 2001, pp. 513-524. 

Physiologically based pharmacokinetic models provide a format to analyze relationships between model parameters and physicochemical properties for a series of drug analogues. Quantitative structure-pharmacokinetic relationships based on PB-PK model parameters have been pursued [12,13] and may ultimately prove useful in the drug development process. In this venue, such relationships, through predictions of tissue distribution, could expedite drug design and discovery. 

Crooke, R.M., In vitro toxicology and pharmacokinetics of antisense oligonucleotides, Anti-Cancer Drug Design, 1991, 6, 609-646. 

The overall accuracy of the predictions, assessed as the mean-fold error of prediction of the test set was 2.03, making this approach one that would possess suitable accuracy for use in drug design and human pharmacokinetic predictions. Similar methods developed separately for acids and bases showed an improvement in accuracy. This investigation also included a prediction of unbound VD, which should represent a simpler parameter to predict since it would be based only on tissue binding and not plasma protein binding. However, it is interesting to note that this approach was less accurate for this parameter, which would be unexpected. 

Imai T. Human carboxylesterase isozymes catalytic properties and rational drug design. Drug Metab Pharmacokinet 2006 21 (3) 173—185. 

Apart from patient-specific parameters, external factors - most importantly the concomitant uptake of certain other chemicals present in diet, environment and especially other drugs - influence drug actions. Possible effects are manifold and can affect all stages of pharmacokinetic and pharmacodynamic processes in the body. Also direct interaction and inactivation of concomitantly administered substances are possible. Drug-drug interactions via modulation of metabolism present a very hot topic in pharmaceutical research and drug design. 

Pharmacokinetics and Metabolism in Drug Design 5 Edited by D. A. Smith, H. van de Waterbeemd, D. K. Walker, R. Mannhold, H. Kubinyi, H. Timmerman I... 

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