Pharmacokinetic Considerations in Rational Drug Design

Abstract

The importance of pharmacokinetic information in the development of a new drug is widely recognised. This information provides a quantitative framework for the evaluation and consideration of factors associated with safety and efficacy. Pharmacokinetic studies in animals have traditionally complemented the evaluation of toxicology (Balant et al. 1990), whereas clinical pharmacokinetic information has been used to optimise therapeutic dosage regimens. Clinical pharmacokinetic data have often revealed sources of variability in the relationship between dose and therapeutic response. Furthermore, clinical data help identify the existence of any factors, such as renal or hepatic disease, that confound the clearance of drugs. Recent technological advances permit rapid collection of pharmacokinetic data and make it likely that provision of such data during the discovery phase of drug development programmes will become routine. Incorporation of pharmacokinetic considerations in drug design will be particularly important for new drug molecules such as peptides, proteins and antisense oligonucleotides.