ABSTRACT
The progression of a drug from animal to human studies probably represents the single most important step in drug development. Investigators should be experienced in the conduct of first-administration studies and familiar with the relevant technique being used to evaluate the biological effect of the drug. The top dose to be used may also be based on animal pharmacology, particularly if the drug to be studied is relatively non-toxic in animal studies. The choice of dosing increments in the escalating dose regimen will be chosen depending on the dose–response relationships in animal studies. These may predict how steep the dose–response curve is likely to be in man and in what dose range the biological effect is likely to be seen. Dose-response relationships within subjects can be determined and the variability in response between subjects can also be addressed. A well-designed first-administration study will allow a dose-response relationship to be identified and will provide preliminary pharmacokinetic data.
