PMID- 14758767
OWN - NLM
STAT- MEDLINE
DCOM- 20040305
LR  - 20211203
IS  - 1472-4472 (Print)
IS  - 1472-4472 (Linking)
VI  - 4
IP  - 11
DP  - 2003 Nov
TI  - Transplantation: toxicokinetics and mechanisms of toxicity of cyclosporine and 
      macrolides.
PG  - 1287-96
AB  - For over two decades, calcineurin inhibitors (CIs) have been the mainstay of 
      immunosuppressive therapy following solid-organ transplantation. However, CI 
      nephrotoxicity is one of the main contributors to chronic kidney allograft 
      dysfunction. A novel class of immunosuppressants that inhibit the kinase 
      mammalian target of rapamycin (mTOR), although not nephrotoxic themselves, 
      enhance CI nephrotoxicity. The biochemical basis of CI toxicity and their 
      toxicodynamic interaction with mTOR inhibitors is still poorly understood. 
      Studies using a magnetic resonance spectroscopy-based metabonomic approach 
      indicate that CI toxicity is caused by drug-induced mitochondrial dysfunction and 
      that mTOR inhibitors enhance the negative effects of CIs on cell energy 
      metabolism.
FAU - Serkova, Natalie
AU  - Serkova N
AD  - Department of Anesthesiology, Clinical Research & Development, University of 
      Colorado Health Sciences Center, 4200 East Ninth Ave, Room UH-2122, Campus Box 
      B113, Denver, CO 80262, USA.
FAU - Christians, Uwe
AU  - Christians U
LA  - eng
GR  - R01 DK065094-01/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - England
TA  - Curr Opin Investig Drugs
JT  - Current opinion in investigational drugs (London, England : 2000)
JID - 100965718
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Macrolides)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Calcineurin Inhibitors
MH  - Cyclosporine/adverse effects/chemistry/*toxicity
MH  - Drug Interactions
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/chemistry/*toxicity
MH  - Kinetics
MH  - Macrolides/adverse effects/chemistry/*toxicity
MH  - *Organ Transplantation
MH  - Protein Kinase Inhibitors
MH  - *Protein Kinases
MH  - TOR Serine-Threonine Kinases
RF  - 77
EDAT- 2004/02/05 05:00
MHDA- 2004/03/06 05:00
CRDT- 2004/02/05 05:00
PHST- 2004/02/05 05:00 [pubmed]
PHST- 2004/03/06 05:00 [medline]
PHST- 2004/02/05 05:00 [entrez]
PST - ppublish
SO  - Curr Opin Investig Drugs. 2003 Nov;4(11):1287-96.