PK-PD理論を基盤とした副作用発現の機構解明とリスクファクターの探索

抄録

The events following drug administration can be divided into two phases: a pharmacokinetic phase (PK) and a pharmacodynamic phase (PD). The pathophysiologic status of patients or concomitant drugs can affect both the PK and PD of a drug. Therefore, it is important to distinguish the effects of several diseases or drugs on the PK from those on the PD. Based on this concept, we studied the mechanism and risk factors of adverse drug reactions using PK-PD analysis. This review summarizes our findings:
1.Renal failure with severe hypotonic hyponatremia is associated with increased central nervous system sensitivity to cephalosporin-induced seizures.
2.Isoniazid potentiates the sensitivity of the central nervous system to cefazolin-induced seizures, and the increased sensitivity is associated with the inhibition of vitamin B6 metabolism by isoniazid.
3.Moxifloxacin can induce histamine release, leading to an increase in serum epinephrine concentrations and hyperglycemia.
4.Hyperglycemic effect of pentamidine is dependent on the concentration of pentamidine and can be enhanced by cimetidine combination.
5.There was large interindividual variability in not only the PK of sunitinib but also the PD of sunitinib-induced thrombocytopenia.
These findings provide useful information for the prevention and management of several adverse drug effects.