[How to measure the kinetics of biological effect of a drug].
Therapeutic benefit that can be induced by a pharmaceutical compound partly relies upon the profile of its biological action. Evaluation of the drug-induced effect profile in a given pathological condition begins with the determination of the relevant biological effect related to the therapeutic benefit, which is not always obvious. Evaluation itself is based on dose-effect relationships as a function of time. During chronic treatment, such a kinetic profile oscillates between peak and trough levels. Relationships that can be established between time-dependent effect profile and pharmacokinetic data lead to PK-PD mathematical model, whose main objectives are simulation, prediction of effect and ultimately dose optimisation. The therapeutic implications of the time-dependent effect profile are well illustrated in the cases of antibiotics, diuretics such as furosemide and anti-hypertensive drugs. During drug development, PK-PD approaches can be used in the initial clinical and even pre-clinical phases and can lead to a better definition of effective dose ranges, optimisation of large scale clinical trials or identification of high risk patients. This may favour a reduction of costs and duration of development. Validation of such an approach is easier in well known therapeutic domains but can be more difficult with innovative drugs. The implications of PK-PD approaches can however, be, limited when the relevant biological or clinical parameter cannot be assessed, when the cascade of events leading to pharmacological and therapeutic effects is complex or finally when such PK-PD models require a long time to be established during the early phase of drug development.
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Pharmacologie Clinique, Groupe Hospitalier, Pitié Salpetrière, Paris, France.
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D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D000959:Antihypertensive Agents / Q000493:pharmacokinetics; D004232:Diuretics / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005665:Furosemide / Q000493:pharmacokinetics; D006801:Humans; D008962:Models, Theoretical; D010599:Pharmacokinetics; D010600:Pharmacology
D000900:Anti-Bacterial Agents; D000959:Antihypertensive Agents; D004232:Diuretics; D005665:Furosemide