Pharmacologic knowledge can inform clinical decision-making, particularly the dosing and switching decisions made with antipsychotics. Of relevance are the pharmacokinetic (what does the body do to the drug) and the pharmacodynamic (what does the drug do to the body) properties of antipsychotics.The goal of antipsychotic dosing is to achieve sufficient dopa-mine blockade in areas where dopamine excess can lead to psychosis, mania, or aggression. Using positron emission topography, one investigation showed that response rates were considerably higher in patients who achieved >65% striatal dopamine blockade. Conversely, striatal dopamine blockade >80% predicted the emergence of extrapyramidal symptoms (EPS) or akathisia.There is, however, considerable intra-individual variability in achieving the desired 60% to 80% striatal dopamine blockade. Such variability is likely due to inter-individual differences in the absorption, distribution, metabolism and elimination of medications. At the same time, antipsychotics themselves differ in their general pharmacokinetic profiles. For example, ziprasidone absorption is ~50% less when ingested on an empty stomach than when taken with a meal; the degree of absorption depends on the caloric content, while the fat content is not relevant.
