Determination of drug dosage

When novel drugs are developed, PET method is very useful in determining suitable drug dosage (Wong et al., 2009).

Drug-induced receptor occupancy, or enzyme inhibition, is measured with PET at different drug plasma concentrations. Occupancy or inhibition is plotted as a function of drug concentration in plasma, and a function may be fitted to the curve. This curve can be accomplished with relatively few subjects and PET studies.

  1. Inhibition or occupancy is measured as a function of steady-state plasma concentration of the drug
  2. Fit a function, for example Hill function (Eq. 1, assuming that γ=1)
  3. Estimate the drug steady-state concentration that leads to desired (usually >90%) enzyme inhibition or receptor occupancy.

Inhibition versus plasma concentration
Figure 1. Inhibition versus plasma concentration.

With pharmacokinetics studies (without PET), with considerably more study subjects, we can then determine the oral drug dosage that leads to required plasma concentration.

Plasma concentration versus drug dose
Figure 2. Plasma concentration versus drug dose.

Combining PET and pharmacodynamic studies we can determine the drug dosage that leads to required enzyme inhibition or receptor occupancy.

See also:


Bretz F, Hsu J, Pinheiro J, Liu Y. Dose finding - a challenge in statistics. Biom J. 2008; 50(4): 480-504. doi: 10.1002/bimj.200810438.

Fischman AJ, Alpert NM, Rubin RH. Pharmacokinetic imaging - a noninvasive method for determining drug distribution and action. Clin Pharmacokinet. 2002; 41(8): 581-602. doi: 10.2165/00003088-200241080-00003.

Matthews PM, Rabiner EA, Passchier J, Gunn RN. Positron emission tomography molecular imaging for drug development. Br J Clin Pharmacol. 2012; 73(2): 175-186. doi: 10.1111/j.1365-2125.2011.04085.x.

Wong DF, Tauscher J, Gründer G. The role of imaging in proof of concept for CNS drug discovery and development. Neuropsychopharmacology 2009; 34(1): 187-203. doi: 10.1038/npp.2008.166.

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Updated at: 2021-02-19
Created at: 2011-11-21
Written by: Vesa Oikonen