PK/PD Relationship

Pharmacokinetics describes what the body does to a drug and pharmacodynamics what the drug does to the body; the PK/PD relationship is the model joining them. Its usual core is a concentration-effect curve of the Emax form, effect rising toward a maximum as concentration climbs past the half-maximal value. When effect lags concentration, a hypothetical effect compartment is added, and a plot of effect against plasma concentration traces a loop rather than a line.

With peptides the lag is often enormous. A single growth hormone injection clears from plasma within hours, but IGF-1 rises over the following day and stays elevated for several days, so plasma growth hormone at any moment says little about effect. With GLP-1 receptor agonists, glycated haemoglobin responds over months because it reflects roughly the preceding three months of glycaemia, and body weight in the STEP and SURMOUNT programmes was still falling at a year.

The relationship is what lets a sponsor choose a phase 3 dose from phase 2 exposure data, predict a regimen never actually tested, and justify a dosing interval on something other than convenience. It also marks the limit of what exposure data can prove: matching concentrations between two products supports matching effect only when the concentration-effect link is the same for both.

The error to watch for is inferring duration of action from half-life, which the growth hormone case refutes outright. The other is the in-vitro potency claim. A compound with an impressive nanomolar EC50 in a cell assay has no clinical meaning unless achievable plasma concentrations, corrected for protein binding, approach that value, and for many research peptides they never do.