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PK-PD modeling

PK/PD modeling (pharmacokinetic/pharmacodynamic modeling) (alternatively abbreviated as PKPD or PK-PD modeling) is a technique that combines the two classical pharmacologic disciplines of pharmacokinetics and pharmacodynamics.[3] It integrates a pharmacokinetic and a pharmacodynamic model component into one set of mathematical expressions that allows the description of the time course of effect intensity in response to administration of a drug dose. PK/PD modeling is related to the field of pharmacometrics. The rationales for in vivo PK-PD-efficacy relationship studies in preclinical models are to:

  1. provide a quantitative analysis of dose–response relationships;
  2. describe and predict the time-course effects resulting from one or multiple drug doses;
  3. understand for how long and how much the target must be modulated to observe statistically significant efficacy;
  4. Ultimately identify efficacious dosing regimens with an acceptable therapeutic index.

Inclusion in vivo PK-PD-efficacy studies at early stages during the lead identification and optimization stages of a drug development program can significantly accelerate the selection of the most promising compounds. This is done by informing on the precise mechanisms of action and by rapidly identifying unexpected toxicity and/or off-target activities in vivo.                                                                                                                               Properly planned and executed PK-PD-efficacy studies requires a team of experts in:

  1. The establishment of the most relevant and appropriate animal model(s);
  2. Animal dosing and handling;
  3. The measurement of efficacy in different models;
  4. The identification of the most appropriate PD readout for the drug and for the model being tested;
  5. The design, optimization and execution of quantitative PD assays and/or measurements;
  6. The measurement of drug concentrations in different tissue matrices;
  7. the evaluation and analysis of PK data;
  8. the analysis of relationships between PK, PD and efficacy.

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