点眼薬の中枢神経系影響のリスク評価: 既存の情報に基づく考察

抄録

The systemic dose levels of eye-drop drugs are relatively low in comparison with that of systemic route such as oral administration. We undertook risk assessment for the central nervous system (CNS) effects of eye-drop drugs, by comparing the estimated systemic dose level of eye-drop drugs with the oral dose levels of known CNS toxicants and CNS medicines (e.g., clinically used drugs of sleeping, antidepressant, antiepileptic, anti-Parkinson diseases and analgesics) of approximately 50 different modes of action (MOAs). The systemic dose levels of eye-drop drugs in human were estimated to be 0.01 to 1.0 mg/body on the assumption of 0.01% to 1% of eye-drop formulation, 0.05 mL/eye of instillation volume, administration to both eyes, 50 kg body weight, and once a day.

As the result, (1) 0.01% eye-drop drug systemic dose level was lower than the efficacy doses of all MOAs; (2) Among the MOAs investigated, the efficacy dose levels of 8 MOAs were located at the relatively low position, which was approximately x10 to x100 dose ratio against 0.01% eye-drop drug systemic dose level; (3) Even at the 1% eye-drop drug systemic dose level, it was 10- to 100-fold lower than that of approximately half of MOAs investigated.

In conclusion, our present investigation strengthens a general consideration that the risk of CNS effect in eye-drop drugs is generally low. Especially, the concentration level of 0.01% or below have less risk of CNS effects in most MOAs. This result also supports the ICH S7A guideline for mentioning unnecessity of safety pharmacology studies for eye-drop drugs.