PMID- 20517177
OWN - NLM
STAT- MEDLINE
DCOM- 20100810
LR  - 20151119
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 90
IP  - 1
DP  - 2010 Jul 15
TI  - Optimal everolimus concentration is associated with risk reduction for acute 
      rejection in de novo renal transplant recipients.
PG  - 31-7
LID - 10.1097/TP.0b013e3181de1d67 [doi]
AB  - BACKGROUND: Everolimus (Evl) plus tacrolimus (Tac) in de novo renal 
      transplantation is effective and safe. Whether the concentration of Evl affects 
      efficacy and safety in a Tac-based regimen has not been previously reported. AIM: 
      To evaluate whether the concentration of Evl affects biopsy-proven acute 
      rejection (BPAR), renal function, adverse events (AEs); and to assess for 
      pharmacokinetic (PK) interactions. METHODS: Data were from a prospective, 
      multicenter, open-label, randomized, exploratory 6-month study of 92 renal 
      transplant patients treated de novo with concentration-controlled Evl (target 
      trough levels > or =3 ng/mL) plus low-dose Tac or Evl plus standard-dose Tac; 
      both groups received basiliximab and corticosteroids. Data were pooled across 
      study arms to examine BPAR rates in patients with Evl trough levels less than 3 
      (n=26), 3 to 8 (n=62), or more than 8 ng/mL (n=4). Groups were stratified by both 
      Evl and Tac trough levels to evaluate glomerular filtration rate and AEs. Evl and 
      Tac PK interactions were evaluated in a subset of 14 patients. RESULTS: Evl 
      trough level of more than or equal to 3 ng/mL was associated with significantly 
      lower rates of BPAR as compared with a trough level of less than 3 ng/mL. 
      Glomerular filtration rate was similar at 6 months for both the low and standard 
      Tac groups. No apparent PK interactions were observed between Evl and Tac. AEs 
      were infrequent and did not seem to be associated with the Evl or Tac level. 
      CONCLUSIONS: Evl trough levels > or =3 ng/mL plus Tac are associated with low 
      rates of BPAR without adversely affecting renal function. No evident PK 
      interaction exists between Evl and Tac.
FAU - Chan, Laurence
AU  - Chan L
AD  - Health Sciences Center, Anschutz Medical Campus, University of Colorado, Denver, 
      CO, USA. larry.chan@ucdenver.edu
FAU - Hartmann, Erica
AU  - Hartmann E
FAU - Cibrik, Diane
AU  - Cibrik D
FAU - Cooper, Matthew
AU  - Cooper M
FAU - Shaw, Leslie M
AU  - Shaw LM
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Immunosuppressive Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - W36ZG6FT64 (Sirolimus)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Adult
MH  - Biopsy
MH  - Cadaver
MH  - Drug Therapy, Combination
MH  - Everolimus
MH  - Female
MH  - Graft Rejection/epidemiology/pathology/*prevention & control
MH  - Humans
MH  - Immunosuppressive Agents/pharmacokinetics/*therapeutic use
MH  - Kidney Failure, Chronic/*drug therapy/etiology
MH  - Kidney Transplantation/*immunology
MH  - Living Donors
MH  - Male
MH  - Middle Aged
MH  - Sirolimus/*analogs & derivatives/pharmacokinetics/therapeutic use
MH  - Tacrolimus/pharmacokinetics/*therapeutic use
MH  - Tissue Donors/statistics & numerical data
EDAT- 2010/06/03 06:00
MHDA- 2010/08/11 06:00
CRDT- 2010/06/03 06:00
PHST- 2010/06/03 06:00 [entrez]
PHST- 2010/06/03 06:00 [pubmed]
PHST- 2010/08/11 06:00 [medline]
AID - 10.1097/TP.0b013e3181de1d67 [doi]
PST - ppublish
SO  - Transplantation. 2010 Jul 15;90(1):31-7. doi: 10.1097/TP.0b013e3181de1d67.