Skipping a pillar does not make for strong foundations: Pharmacokinetic-pharmacodynamic reasoning behind the shape of dose-response relationships in oncology.

ABSTRACT: Dose-response analysis is often applied to the quantification of drug-effect especially for slowly responding disease end points where a comparison is made across dose levels after a particular period of treatment. It has long been recognized that exposure - response is more appropriate than dose-response. However, trials necessarily are designed as dose-response experiments. Second, a wide range of functional forms are used to express relationships between dose and response. These considerations are also important for clinical development because pharmacokinetic (PK; and variability) plus pharmacokinetic-pharmacodynamic modeling may allow one to anticipate the shape of the dose-response curve and so the trial design. Here, we describe how the location and steepness of the dose response is

SUBMITTER: Yates JWT 

PROVIDER: S-EPMC10681527 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature