Dose escalation schedule (revision 2)
Old revision·09:24, 14 Oct 2024·A1c_Alder
| Dose escalation schedule | |
|---|---|
| Purpose | Tolerability, not efficacy |
| Typical step interval | 4 weeks for weekly agents |
| Limiting effect | Gastrointestinal adverse events |
| Topic infobox · conventions | |
A dose escalation schedule is a planned stepwise increase from a starting dose to a maintenance dose. For incretin agonists it exists to manage tolerability: the starting dose is generally below the effective range, and its purpose is to allow gastrointestinal adaptation before an effective dose is reached.[1]
Step intervals for weekly agents are conventionally four weeks, which is approximately the time to steady state for a peptide with a half-life of several days. Escalating faster raises the dose before the previous step is fully expressed, so both exposure and adverse effects accumulate.[2]
Why escalation works
[edit]Nausea and vomiting from incretin agonism attenuate with continued exposure at a constant dose, an adaptation associated with the attenuation of the delay in gastric emptying over the same period. Escalation exploits that adaptation by holding each dose long enough for it to occur before increasing.[1]
The insulinotropic and appetite effects do not attenuate in the same way, so the adaptation is selective: tolerability improves while efficacy is retained. This asymmetry is what makes the strategy work at all.