title: Predictive value of phase I studies: relevant criteria.
abstract: Phase I studies cannot predict the therapeutic efficacy of a new drug. However, they can lead to important information concerning: i), the undersirable 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.
authors.affiliation: Department of Physiology and Clinical Pharmacology, URA CNRS 606, Faculty of Pharmacy, Lyon, France.
authors.forename: J
authors.initials: J
authors.lastname: Sassard
authors.forename: N
authors.initials: N
authors.lastname: Pozet
authors.forename: N
authors.initials: N
authors.lastname: Bernard
authors.forename: N
authors.initials: N
authors.lastname: Ferry
authors.forename: G
authors.initials: G
authors.lastname: Cuisinaud
mesh_terms: D004341:Drug Evaluation; D004358:Drug Therapy; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D010599:Pharmacokinetics