Drug handling predicting

III. How Important Are Genetic Variants in Predicting Drug Handling ... 

This model has been used to predict what might happen to drug handling and dose requirements under different clinical circumstances by categorising drugs according to their extraction ratio [1]. 

Chronic alcohol consumption can induce CYP450 enzymes, whereas acute alcohol intake can inhibit cytochrome P450 enzymes. Prediction of drug handling in alcoholic liver disease is therefore complicated. 

Therefore, estimation of plasma concentrations, and how they are altered by the many factors that can affect drug handling, may be used to make predictions about dosage in the otherwise healthy individual and in the presence of organ failure or concomitant medications. 

The challenge for the drug discovery organization is how to handle the resource issues for multiple screening data feedback. Often a combination of experimental screens and computational prediction approaches will be used. Rapid data feedback to the medicinal chemist is essential, whether the data is experimental or computational. Data delayed is data with greatly reduced value. 

Reconstituted HCE (order no. RHC/S/5) is available from Skinethic, Nice, France. It consists of transformed human corneal epithelial cells immortalized by Roger Beuerman from the Louisiana State University-Eye Center, New Orleans, USA. This reconstituted human corneal epithelium forms a multilayered cell culture model that does not exhibit tight junctions and is therefore unsuitable for in vitro drug transport studies. Main focus of the model is eye irritation and toxicity testing and it is commonly used in this area with good prediction qualities. Major advantage of this model is the high reproducibility and uniform appearance. The commercial availability provides a ready-to-use model that is easy to handle. 

The pharmacokinetics of a drug in rodents, dogs and primates are certainly of some predictive value to humans, although there can often be surprises. If there is good agreement between species, it is likely that humans will handle the drug in a similar fashion. Conversely, if the major clearance mechanism, metabolic or... 

The half-life determines the time it will take to achieve steady state and is useful for determining a dosing regimen. However, it does not give any clue to the processes involved in handling the drug, so that knowledge of the half-hfe alone cannot be used to make predictions about factors which are likely to affect the rate of elimination. 

Those who have worked through earlier parts of this chapter will have no difficulty in predicting that the body is likely to treat chemicals from plant sources as just one more set of chemical invaders that should be handled in exactly the same way as foods and Western-style medicinal drugs. 

Nassar, A. E., and Adams, P. E. (2003). Metabolite characterization in drug discovery utilizing robotic liquid-handling, quadruple time-of-flight mass spectrometry and in-silico prediction. Curr. Drug. Metab. 4 259-271. 

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