Kurzfassung

A new insight to drug pharmacokinetic and pharmacodynamic variability relates to active drug transportation most often carried out across biological barriers, such as the blood-brain-barrier (BBB), for many psychoactive drugs. Under normal circumstances a regular distribution of a prominent drug transport protein like the P-glycoprotein (P-gp) will be responsible for a “normal” clearing of drugs that have entered from the blood to an effect compartment. In our case, a lack of the...A new insight to drug pharmacokinetic and pharmacodynamic variability relates to active drug transportation most often carried out across biological barriers, such as the blood-brain-barrier (BBB), for many psychoactive drugs. Under normal circumstances a regular distribution of a prominent drug transport protein like the P-glycoprotein (P-gp) will be responsible for a “normal” clearing of drugs that have entered from the blood to an effect compartment. In our case, a lack of the polymorphically expressed human ABCB1-gene (the multidrug resistance-1; MDR1 transporter gene) will provide a basis for an abnormal (low) distribution of the P-gp. This could lead to an increased gradient of drug in brain versus that in blood on a genetic basis, since the function of P-gp is to actively “pump out” a number of drugs from the brain. A similar effect could appear as a phenotypic consequence if, for example, a strong inhibitor of the P-gp (like the immunosuppressant drug ciclosporin-A) is present. In order to add also this factor to the list of tentative parameters for obscuring simple drug blood concentrations versus clinical effects of psychoactive drugs, we plan to investigate the genetic as well as phenotypic outcome in different study designs for the many psychoactive drugs available. » weiterlesen» einklappen