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If a PO drug is selected for a QD dosing what kind PK parameters
(T1/2, Cmax, CL, Vd, AUC, %F) should be critical and their values? The
dosing route will be by oral delivery. The compound is eficacious at
lower dose levels.
Thank you
Anila
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The following message was posted to: PharmPK
Hi Anila,
What parameter would be the most relevant depends on how the compound exerts its effect and there are other parameters you have not mentioned in your e-mail. If you have a direct relation between your drug concentrations and the effect you are interested in, i.e. once you have drug you see effect and when the drug is gone your effect is also gone, some PK parameters you mentioned may guide you in your dosing. Depending on the potency of your compound, you may not need much drug around for your effect so you may be able to wait more than a half-life with the next dose. This will depend on your therapeutic window, i.e., how high concentrations you can have without side-effects and how low concentrations you may go without losing the effect.
It becomes certainly more interesting when the relation between drug concentrations and the observed effect are not as straight forward as the example above. Your drug may have a hit-and-run type of effect, i.e., it starts some process but then does not need to be around for the system to live its own life. In this case you will need to characterize the system to know how fast the onset of the effect is and how long it takes for it to go back to its pre-dose state. If you know that, you can modify your dosing regimen.
In my opinion, the best way to find out what dose and dosing frequency you will need is to build a PK/PD model, where you characterize the drug kinetics, the kinetics of your effect, and the relation between the drug concentrations and the observed effect. Once you have the model in place, it is rather simple to test different scenarios (q.d. or b.i.d., x mg or 10x mg) in your computer. You can even find out what parameter would be the most important one, if someone asks you for a single parameter.
Toufigh Gordi, PhD
Clinical Pharmacology, PK/PD analysis consultant
www.tgordi.com
E-mail: tg.-a-.tgordi.com
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