Foreword

Therapeutic drug monitoring (TDM) was introduced in clinical practice in 1980 when the measurement of serum concentration of lithium carbonate became covered by health insurance in Japan. In June of the following year, a specific “drug management fee” was newly introduced in the health insurance, and TDM for digitalis and antiepileptic drugs was also started. Since then, TDM for more than 40 types of drugs; mainly immunosuppressants, anti-infectives, and antiarrhythmic drugs, has been covered by health insurance if specific requirements are met. Thus, TDM has been used in routine clinical practice.

On the other hand, TDM is recommended for many drugs even though the procedure is not covered by health insurance. Imatinib and sunitinib as molecular targeted drugs have recently been covered by insurance. Furthermore, many clinical studies have provided evidence for the usefulness of TDM not only for epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and multikinase inhibitors, but also for some immunomodulators, and the target plasma concentration ranges are being established.

As for anti-infective agents, the only drugs currently covered by health insurance for TDM are glycopeptides, aminoglycosides, and voriconazole. However, in recent years, the need for TDM has been advocated not only for itraconazole, for which TDM has been recommended for a long time, but also for some drugs including linezolid and β-lactam antibiotics in intensive care settings. Regarding antipsychotics and antidepressants, there are active movements in Japan and overseas countries to strongly recommend TDM for many drugs including tricyclic antidepressants, some selective serotonin reuptake inhibitors, and clozapine. Since antibody drugs are structurally similar to immunoglobulin G in living organisms, the variation in pharmacokinetics between individuals is conventionally considered small. However, it has become clear in recent years that individual differences are observed in the pharmacokinetics of some antibody drugs such as infliximab and rituximab, and the usefulness of TDM is being proposed.

Given this background, this Current Topic focuses on four areas: (1) anticancer drugs, (2) anti-infective agents, (3) antipsychotics/antidepressants, and (4) antibody drugs. Among the drugs that are not approved for insurance coverage in Japan, the drugs for which TDM is recommended and drugs that are likely to be approved in the future are summarized in a review, which include their pharmacokinetic characteristics and the usefulness of TDM. We hope that this Current Topic will contribute to the expansion of insurance-covered TDM for more drugs in Japan and further development of personalized medicine in the future.