Is it possible for a drug that it's duration of action time be bigger than it's clearance time?
Yes, surely. It depends on the mechanism of action. The simplest example is ASA and the inhibition of platelets. The ASA is gone in hours (salicylic acid), the inhibition of platelets lasts for days because it`s irreversible.
Hi,
It's the situation when the clinical effect has no simple link with target receptor occupancy. Very often observed in therapeutic monoclonal antibodies (mAbs). Especially in mAbs, we can distinguish the mechanism of action (saturation of target receptor) and mode of action (effect of interaction with a receptor). The mode of action in many drugs is not explained and we still learn more about that.
If the clinical effect is dependent on the mode of action cascade of effects then the clinical effect can persist or be visible even if the saturation of the target receptor is very low.
If the mode of action has an impact on clinical effect but dosing was proposed based on the relationship between PK profile and receptor occupancy then you can observe the clinical effect longer than explained by the presence of the drug in the bloodstream.
Consequently in many mAbs scientists now suggest extended dosing intervals, see examples below:
4 → 6-8 weeks (natalizumab) 2
12 → 24 weeks (ustekinumab) 3
2 → 4 weeks (adalimumab) 4
1 → 2 weeks (etanercept) 5
4 → 5-6 weeks (tocilizumab) 6
4 → 8 weeks (atezolizumab) 7
8 → 12 weeks (infliximab) 8
2 DOI: 10.1177/ 1756285614540224
3 DOI: 10.1111/bjd.15722
4 DOI: 10.1136/bmjopen-2019-035326
5 DOI: 10.1097/FTD.0000000000000420
6 PMID: 28229812
4 DOI: 10.1136/bmjopen-2019-035326
5 DOI: 10.1097/FTD.0000000000000420
6 PMID: 28229812
7 DOI: 10.1007/s00228-020-02980-3
8 . doi:10.1136/bmjopen-2021-054154
Best regards
Tomasz
As a general rule, the duration of action of a drug is proportional to its clearance time. Clearance refers to the rate at which a drug is removed from the body, which is typically a function of both its metabolism and elimination from the body. A drug with a faster clearance rate will have a shorter duration of action compared to a drug with a slower clearance rate.
However, it is possible for a drug to have a duration of action time that is bigger than its clearance time. This occurs when the concentration of the drug in the body remains above the therapeutic threshold for a longer period than it takes for the drug to be cleared from the body. This can be due to the drug's pharmacokinetics, such as a slow release or a long half-life, or it can be due to the drug's pharmacodynamics, such as a long lasting effect on the target receptors.
In summary, while the duration of action of a drug is usually proportional to its clearance rate, there are exceptions to this rule.
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