Objective: Clinical trials are designed to clarify the dose-dependency of drugs.  However, the dose-dependency of adverse drug reactions (ADR), especially in the subtherapeutic range, often remains unclear.  Whether decreasing a drug’s dose would reduce the risk of ADR is of interest to both clinicians and regulators.  This study aimed to clarify the dose-dependency of ADR during subtherapeutic exposure to non-steroidal anti-inflammatory drugs, immunosuppressants, β-adrenoceptor antagonists, or corticosteroids.
Methods: Data about the ADR risk profiles and the area under the concentration curve (AUC) values of the examined drugs during their subtherapeutic administration, e.g., after their topical or low-dose oral administration, were collected from the literature and compared with data obtained during the therapeutic administration of the drugs; i.e., at the standard oral dosage.
Results: The drugs that exhibited AUC of ≥20% during their therapeutic administration continued to cause significant systemic ADR during their subtherapeutic administration.  Whilst the drugs that demonstrated AUC of 3-20% during their therapeutic administration continued to cause systemic ADR during their subtherapeutic administration, the ADR tended to be less frequent.
Conclusion: The dose-dependency of ADR can be estimated by comparing the AUC and ADR risk profile data for a drug obtained during its topical, parenteral, or low-dose oral administration with that obtained during its oral administration at the standard dose.  However, some studies have detected high ADR frequencies even during reduced systemic exposure, suggesting that factors affecting the risk of ADR, e.g., patients’ background data, should be carefully matched between the datasets being compared.

Background: Although transferring drugs to a third party, even in a personal capacity, is illegal in Japan, many drug transactions are carried out via internet auction sites. Pharmacy consumers might not be aware of the illegality of transferring drugs to others due to various factors. To clarify pharmacy consumers’ awareness of this issue and its covariates, we carried out a questionnaire survey.Methods: A self-completed questionnaire, consisting of yes/no and multiple-choice questions, was used. The adult patients who visited Keio University Pharmacy were asked to fill out the questionnaire.Results and Discussion: One hundred and fifty-one response sheets were effectively collected from 173 responders. The subjects’awareness of the illegality of transferring drugs was significantly affected by the formulation (oral vs. patches) and pharmacological category of the drug, as well as the source of the drug (prescribed vs. over the counter). Patient education about the illegality of personally transferring drugs, especially patches, might be required to avoid illegal drug transfers, including via the internet.