소소한 일상 기록

The extent of drug exposure or concentration in the active site is related to its effect. Too low concentration of a drug will cause no therapeutic effect, and too high concentration will cause serious adverse effects. The idea of pharmacokinetics was developed before technology could detect drug molecules in the body fluids.

There were many approaches to describe kinetics of drugs in human body using in vitro or in vivo data. Allosteric approach was a simple one. Body-surface area, body weight, brain weight or expected life time were used to extrapolate data. However it was too much simplified approach. Compartment model is another approach to describe kinetics of drug. It can interpret and predict drug concentration of the compartment. But as a compartment is not an anatomical organ or tissue, this model could not reflect physiological characters and predict organ or tissue concentrations of drug.

Advance in computers made us able to handle more compartments. With the ability, whole-body physiological model, called Whole-Body Physiologically Based Pharmacokinetics (PBPK) Model, was developed to reflect physiological character of our body from empirical semi-mechanistic compartment model. Each compartment of the model represents an organ or tissue. Arrows reflect blood flow or elimination in mechanistic way.

In principle, a PBPK model can predict kinetics of drug based on drug-independent or drug-dependent prior data parameters. As it is more mechanistic model than empirical compartment model, this model has much power and utility to predict the extent of drug interactions. Using PBPK modeling, health and medical professionals are able to convey extensive personalized pharmacotherapy to their patients, and pharmaceutical companies can efficiently predict potential interactions of molecules under development.

References

  1. Espié, P. et al. (2009). Drug Metabolism Reviews, 41(3), 391-407. doi: 10.1080/10837450902891360
  2. Rowland, M. et al. (2012). J Pharm Sci, 101(11), 4075-4099. doi: 10.1002/jps.23295

 

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