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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 th...

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Autores principales: Shimada, Hideyo, Yono, Makoto, Hojo, Yuya, Hamamura, Yuka, Ootsuki, Atsushi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Asia Pty Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217045/
https://www.ncbi.nlm.nih.gov/pubmed/31696635
http://dx.doi.org/10.1111/luts.12295
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author Shimada, Hideyo
Yono, Makoto
Hojo, Yuya
Hamamura, Yuka
Ootsuki, Atsushi
author_facet Shimada, Hideyo
Yono, Makoto
Hojo, Yuya
Hamamura, Yuka
Ootsuki, Atsushi
author_sort Shimada, Hideyo
collection PubMed
description 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.
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spelling pubmed-72170452020-05-13 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 Shimada, Hideyo Yono, Makoto Hojo, Yuya Hamamura, Yuka Ootsuki, Atsushi Low Urin Tract Symptoms Original Articles ‐ Clinical 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. Blackwell Publishing Asia Pty Ltd 2019-11-06 2020-05 /pmc/articles/PMC7217045/ /pubmed/31696635 http://dx.doi.org/10.1111/luts.12295 Text en © 2019 The Authors. LUTS: Lower Urinary Tract Symptoms published by John Wiley & Sons Australia, Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles ‐ Clinical
Shimada, Hideyo
Yono, Makoto
Hojo, Yuya
Hamamura, Yuka
Ootsuki, Atsushi
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Original Articles ‐ Clinical
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217045/
https://www.ncbi.nlm.nih.gov/pubmed/31696635
http://dx.doi.org/10.1111/luts.12295
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