Premium
Predictive value of phase I studies: relevant criteria
Author(s) -
Sassard J.,
Pozet N.,
Bernard N.,
Ferry N.,
Cuisinaud G.
Publication year - 1990
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1990.tb00063.x
Subject(s) - drug , pharmacokinetics , pharmacodynamics , pharmacology , medicine , drug metabolism , drug interaction , predictive value , efficacy , therapeutic effect , drug development
Summary— Phase I studies cannot predict the therapeutic efficacy of a new drug. However, they can lead to important information concerning: i), the undesirable effects and their mechanisms of occurrence; and ii), the pharmacokinetics and the metabolism of the drug as well as their possible alterations in renal or hepatic diseases. When considering the therapeutic effects, 3 cases have to be considered which are, in order of decreasing predictive value: i), when a direct relationship is expected between the drug concentration in the body and its therapeutic effects ( eg , antibiotics); ii), when the drug has a known molecular or cellular target which is directly involved in the pathophysiology of the disease ( eg , renin inhibitors); and iii), when the drug does not have a known target or is directed toward a precise target which is not directly involved in the disease. In all these cases, a phase I study in healthy volunteers should be able to describe, at least qualitatively, the pharmacodynamic effects of the drug which are relevant to its therapeutic goal.