[Clinical pharmacology and pharmacoepidemiology for medication safety in clinical settings]

In this review, optimization of individualized analgesic therapy in cancer-pain patients (1), pharmacoepidemiological studies using a hospital database (DB) (2), and other clinical and practical research studies (3) were summarized. (1) The aim of the analgesic study was to evaluate individual factors in the effects of pain-relief, and ADR of analgesics from the viewpoints of clinical pharmacokinetics and pharmacodynamics. Oxycodone, fentanyl, and gabapentin were used. For the dose escalation and ADR of oxycodone, the plasma disposition of noroxycodone regulated by CYP3A5 polymorphisms and cancer cachexia were found to be individual factors. The ADR and clinical response of fentanyl were affected by polymorphisms of CYP3A5 and ABCB1. In the pharmacokinetics of gabapentin, concomitant magnesium oxide reduced the intestinal absorption of gabapentin. (2) The aim of the DB study was to demonstrate a pharmacoepidemiological advantage using a hospital DB of a million-scale for post-marketing safety management. We tried to detect fluoroquinolone (FQ)-induced tendon disorders, because its risk ratio in Japan has not been clarified. The risk of a tendon disorder in FQ-prescribed patients was 0.082% (95%CI: 0.049-0.137%), and significantly higher than that in cephalosporin-prescribed patients. The risk ratio in FQ-prescribed patients in relation to cephalosporin-prescribed patients was 6.29 (95%CI: 2.27-17.46). (3) Individual variation of plasma exposure of free linezolid and its ratio to minimum inhibitory concentration in critically ill patients, as well as three other studies, were described. In conclusion, our achievement in accurately assessing these would contribute to medication safety and the appropriate use of medicines in clinical settings.