PMID- 27340909
OWN - NLM
STAT- MEDLINE
DCOM- 20190416
LR  - 20190416
IS  - 1536-3686 (Electronic)
IS  - 1075-2765 (Linking)
VI  - 26
IP  - 1
DP  - 2019 Jan/Feb
TI  - The Effect of Concomitant Sirolimus and Propofol Therapy on Triglyceride 
      Concentrations in Critically Ill Patients.
PG  - e103-e109
LID - 10.1097/MJT.0000000000000461 [doi]
AB  - BACKGROUND: Sirolimus and propofol are both independently associated with the 
      development of hypertriglyceridemia (HTG) during therapy. To date, there are no 
      published reports describing synergistic or additive drug interaction resulting 
      in HTG with concomitant use of these medications. STUDY QUESTION: To identify the 
      occurrence of HTG in patients receiving concomitant sirolimus and propofol 
      infusion therapy. METHODS: Adult patients receiving sirolimus and a continuous 
      propofol infusion for at least 12 hours from January 2005 to August 2009 were 
      retrospectively evaluated. Data included Acute Physiology and Chronic Health 
      Evaluation II score, weight, length of propofol therapy, and baseline 
      triglyceride (TG) concentrations. The major outcome was incidence of HTG (TGs 
      >/=500 mg/dL). Minor outcomes included the change in TG concentration from therapy 
      initiation and manifestations of propofol-related infusion syndrome (PRIS). 
      RESULTS: Sixteen patients were included in the analysis, with 8 (50%) of the 
      patients developing HTG. The patients in this case series had the following mean 
      values: Acute Physiology and Chronic Health Evaluation II score of 20.2 +/- 5.3, 
      weight of 76.3 +/- 21.2 kg, and baseline TG concentrations of 181.3 +/- 89.7 mg/dL. 
      Indications for sirolimus therapy included hematopoietic stem-cell 
      transplantation (n = 15) and heart transplantation (n = 1). Mean length of 
      propofol infusion was 99.8 +/- 88.5 hours. The mean TG concentration during 
      infusion was 515.6 +/- 468.1 mg/dL. Fourteen (87.5%) patients had an increase of 
      >/=100 mg/dL, 12 (75%) patients had an increase of >/=200 mg/dL, and 6 (37.5%) 
      patients had an increase of >/=300 mg/dL in TG concentrations during therapy. 
      Eleven patients developed one manifestation of PRIS, excluding HTG, and one 
      patient had more than 2 new onset PRIS manifestations during propofol therapy. 
      CONCLUSIONS: Coadministration of propofol and sirolimus can potentially result in 
      HTG, which may warrant more frequent monitoring. Further analysis is needed to 
      examine the mechanism and clinical impact of this interaction.
FAU - Dube, Kevin M
AU  - Dube KM
AD  - Department of Pharmacy, Brigham and Women's Hospital, Boston, MA.
FAU - Szumita, Paul M
AU  - Szumita PM
AD  - Department of Pharmacy, Brigham and Women's Hospital, Boston, MA.
FAU - Rocchio, Megan A
AU  - Rocchio MA
AD  - Department of Pharmacy, Brigham and Women's Hospital, Boston, MA.
FAU - Lee, Po-Shun
AU  - Lee PS
AD  - Executive Vice President, Chief Medical Officer, Proteostasis Therapeutics, Inc., 
      Cambridge, MA.
FAU - Anger, Kevin E
AU  - Anger KE
AD  - Investigation Drug Services, Department of Pharmacy, Brigham and Women's 
      Hospital, Boston, MA.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Ther
JT  - American journal of therapeutics
JID - 9441347
RN  - 0 (Triglycerides)
RN  - W36ZG6FT64 (Sirolimus)
RN  - YI7VU623SF (Propofol)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Critical Illness/*therapy
MH  - Drug Interactions
MH  - Drug Synergism
MH  - Drug Therapy, Combination/adverse effects/methods
MH  - Female
MH  - Humans
MH  - Hypertriglyceridemia/blood/*chemically induced/diagnosis/epidemiology
MH  - Incidence
MH  - Intensive Care Units/statistics & numerical data
MH  - Male
MH  - Middle Aged
MH  - Propofol/*adverse effects
MH  - Propofol Infusion Syndrome/blood/diagnosis/*epidemiology/etiology
MH  - Retrospective Studies
MH  - Sirolimus/*adverse effects
MH  - Triglycerides/*blood
EDAT- 2016/06/25 06:00
MHDA- 2019/04/17 06:00
CRDT- 2016/06/25 06:00
PHST- 2016/06/25 06:00 [pubmed]
PHST- 2019/04/17 06:00 [medline]
PHST- 2016/06/25 06:00 [entrez]
AID - 10.1097/MJT.0000000000000461 [doi]
PST - ppublish
SO  - Am J Ther. 2019 Jan/Feb;26(1):e103-e109. doi: 10.1097/MJT.0000000000000461.