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Comment
. 2022 Jul;62(7):833-834.
doi: 10.1002/jcph.2051. Epub 2022 Apr 20.

Commentary on Pharmacologically Meaningful Half-Life

Nick Holford  1
Affiliations
Comment

Commentary on Pharmacologically Meaningful Half-Life

Nick Holford. J Clin Pharmacol. 2022 Jul.
No abstract available

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Conflict of interest statement

The author has no conflicts of interest to declare.

Not applicable.

Figures

Figure 1
Figure 1
Time course of concentration (blue) and effect (red) with a peak concentration equal to C50. The concentration half‐life is about 7 time units. Concentrations are mainly lower than the C50, and thus the effect is approximately proportional to the concentration. The time course of the effect is similar to the time course of concentration, but does not follow the exponential decrease and therefore cannot be described with a half‐life of effect.
Figure 2
Figure 2
Time course of concentration (blue) and effect (red) with a peak concentration equal to 10 × C50. The concentration half‐life is unchanged. The time course of the effect decreases slowly relative to the concentration. It is clearly not exponential and cannot be described with a half‐life of effect.
Figure 3
Figure 3
Time course of concentration (blue) and effect (red) with a peak concentration equal to 100 × C50. The time course of the effect decreases very slowly relative to the concentration. After more than six concentration half‐lives (42 time units) the drug effect is still more than 70% of the maximum. A dosing interval of 48 time units would achieve a substantial drug effect with very little drug accumulation. The choice of dosing interval depends on the drug effect, not the concentration half‐life.
See this image and copyright information in PMC

Comment on

References

    1. Chaikin P, Pai SM. Will the pharmacologically meaningful half‐life please stand up? J Clin Pharmacol. 2022;62(7):829‐832. - PubMed
    1. Holford N. Pharmacodynamic principles and the time course of immediate drug effects. Transl Clin Pharmacol. 2017;25(4):157‐161. - PMC - PubMed