Phase I study of KRP‐116D, a 50% w/w dimethyl sulfoxide aqueous solution, on the systemic absorption from bladder by intravesical instillation in healthy Japanese subjects

OBJECTIVE: This was a single‐institution, single‐dose, single‐arm phase 1 study in healthy adult males to evaluate the safety and absorption of dimethyl sulfoxide (DMSO) from the bladder into the body when KRP‐116D (a 50% w/w DMSO solution) was intravesically administered and allowed to remain in the bladder for 15 minutes. METHODS: Six healthy adult males were enrolled in this study. KRP‐116D (50 mL) was instilled directly into the bladder via a catheter where it was allowed to remain for 15 minutes under lidocaine anesthesia in accordance with the usage of RIMSO‐50 (50% w/w DMSO solution) approved in the USA. The residual DMSO solution in the bladder was collected 15 minutes after instillation. The concentrations of DMSO in the plasma and the recovered solution were analyzed by a validated high‐performance liquid chromatography (HPLC) method. The concentration in the residual DMSO solution was multiplied by the solution volume and divided by the dosage to calculate the recovery rate of DMSO. RESULTS: Plasma DMSO was detected in one of six subjects, and in the remaining five subjects DMSO was not detected (<19.6 μg/mL). The recovery rate of DMSO from the bladder was 60.7% to 93.7%. The only drug‐related adverse event was breath odor (garlic‐like breath) observed in four of six subjects (66.7%). CONCLUSION: Absorption of DMSO from the bladder was low (16.3%), and the systemic exposure was limited. Most of the DMSO was recovered from the bladder. KRP‐116D 50 mL was well tolerated and safe.