PMID- 24548545
OWN - NLM
STAT- MEDLINE
DCOM- 20160919
LR  - 20141022
IS  - 1601-0825 (Electronic)
IS  - 1354-523X (Linking)
VI  - 20
IP  - 8
DP  - 2014 Nov
TI  - Levels of sirolimus in saliva and blood following mouthwash application.
PG  - 768-72
LID - 10.1111/odi.12229 [doi]
AB  - OBJECTIVES: Sirolimus (rapamycin) is a mammalian target of rapamycin (mTOR) 
      inhibitor with antiproliferative activity. Its systemic administration is 
      currently evaluated for the management of squamous cell carcinoma and various 
      oral disorders. Topical oral application can enhance availability, efficacy and 
      improve safety and compliance. Our objective was to evaluate the release profile 
      and the safety of a sirolimus mouthwash. SUBJECTS AND METHODS: A sirolimus 
      mouthwash (0.05 mg ml(-1) ) was applied to ten healthy male volunteers. Saliva 
      and blood samples were taken after rinsing. Mass spectrometry and 
      chemiluminescent microparticle immunoassay were used to determine saliva and 
      blood levels of sirolimus. A topical oral release profile measurement and safety 
      evaluation were performed. RESULTS: After rinsing with the mouthwash, a classic 
      immediate release profile was noted in the oral cavity. Extremely high initial 
      sirolimus levels rapidly declined over a 4-hour period. Systemic exposure was 
      limited, with a maximum level significantly lower than therapeutic doses, and 
      safety was confirmed. CONCLUSIONS: A single rinse with sirolimus mouthwash leads 
      to high transient levels of the drug in the saliva. Although levels were 
      variable, a therapeutic concentration was achieved topically along with minimal 
      systemic absorption. These results broaden the potential clinical use of oral 
      topical rapalogs.
CI  - (c) 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Nudelman, Z
AU  - Nudelman Z
AD  - Department of Pharmaceutics, Faculty of Medicine, The Institute for Drug 
      Research, School of Pharmacy, The Hebrew University, Jerusalem, Israel.
FAU - Friedman, M
AU  - Friedman M
FAU - Barasch, D
AU  - Barasch D
FAU - Nemirovski, A
AU  - Nemirovski A
FAU - Findler, M
AU  - Findler M
FAU - Pikovsky, A
AU  - Pikovsky A
FAU - Gutkind, Js
AU  - Gutkind J
FAU - Czerninski, R
AU  - Czerninski R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140324
PL  - Denmark
TA  - Oral Dis
JT  - Oral diseases
JID - 9508565
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Mouthwashes)
RN  - W36ZG6FT64 (Sirolimus)
MH  - Adult
MH  - Healthy Volunteers
MH  - Humans
MH  - Immunosuppressive Agents/blood/*metabolism
MH  - Male
MH  - *Mouthwashes
MH  - Sirolimus/blood/*metabolism
MH  - Young Adult
OTO - NOTNLM
OT  - local application
OT  - mucositis
OT  - oral cancer
OT  - rapalogs
OT  - safety
EDAT- 2014/02/20 06:00
MHDA- 2016/09/20 06:00
CRDT- 2014/02/20 06:00
PHST- 2013/11/12 00:00 [received]
PHST- 2014/01/28 00:00 [revised]
PHST- 2014/02/06 00:00 [accepted]
PHST- 2014/02/20 06:00 [entrez]
PHST- 2014/02/20 06:00 [pubmed]
PHST- 2016/09/20 06:00 [medline]
AID - 10.1111/odi.12229 [doi]
PST - ppublish
SO  - Oral Dis. 2014 Nov;20(8):768-72. doi: 10.1111/odi.12229. Epub 2014 Mar 24.