PMID- 23859571
OWN - NLM
STAT- MEDLINE
DCOM- 20140317
LR  - 20201209
IS  - 1744-8042 (Electronic)
IS  - 1462-2416 (Linking)
VI  - 14
IP  - 10
DP  - 2013 Jul
TI  - Impact of pharmacogenetics on CNS side effects related to efavirenz.
PG  - 1167-78
LID - 10.2217/pgs.13.111 [doi]
AB  - AIM: This article evaluates which genetic factors are involved in CNS toxicity 
      related to long-term treatment with efavirenz (EFV) standard doses and their 
      relationship with plasma concentrations. PATIENTS & METHODS: A total of 119 
      HIV-positive patients, in which 1350 EFV plasma concentrations, 68 SNPs and 14 
      EFV-related adverse effects (AEs) were analyzed. RESULTS: Overall, 32.77% of 
      patients reported CNS toxicity and 8.40% had concentrations above the therapeutic 
      range. A correlation was mainly found between patients with global CNS AEs and 
      high EFV maximum steady-state plasma concentration (p = 1.47 x 10(-6)). A 
      preliminary analysis confirmed that CYP2B6*6 (516G>T and 785A>G) was the most 
      highly correlated (p = 0.005) with AEs and high plasma concentrations. In a 
      second analysis adjusting for maximum steady-state plasma concentration, 
      suggestive genetic associations were found between BCRP 421C>A, MRP1 816G>A, 
      5-HT2A 102C>T and different AEs. CONCLUSION: The finding of the involvement of 
      these SNPs in EFV toxicity opens the door for further studies to confirm their 
      validity and for their application in the future clinical practice. Original 
      submitted 18 February 2013; Revision submitted 17 May 2013.
FAU - Sanchez Martin, Almudena
AU  - Sanchez Martin A
AD  - Pharmacy Service, University Hospital of Salamanca, Salamanca, Spain.
FAU - Cabrera Figueroa, Salvador
AU  - Cabrera Figueroa S
FAU - Cruz Guerrero, Raquel
AU  - Cruz Guerrero R
FAU - Hurtado, Liliana Porras
AU  - Hurtado LP
FAU - Hurle, Alfonso Dominguez-Gil
AU  - Hurle AD
FAU - Carracedo Alvarez, Angel
AU  - Carracedo Alvarez A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Pharmacogenomics
JT  - Pharmacogenomics
JID - 100897350
RN  - 0 (Alkynes)
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Benzoxazines)
RN  - 0 (Biomarkers, Pharmacological)
RN  - 0 (Cyclopropanes)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (CYP2B6 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2B6)
RN  - JE6H2O27P8 (efavirenz)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Alkynes
MH  - Anti-HIV Agents/administration & dosage/adverse effects
MH  - Aryl Hydrocarbon Hydroxylases/genetics
MH  - Benzoxazines/administration & dosage/*adverse effects/pharmacokinetics
MH  - Biomarkers, Pharmacological
MH  - Central Nervous System Diseases/chemically induced/*genetics
MH  - Cyclopropanes
MH  - Cytochrome P-450 CYP2B6
MH  - Female
MH  - HIV/pathogenicity
MH  - HIV Infections/*drug therapy/genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Pharmacogenetics
MH  - Polymorphism, Single Nucleotide
EDAT- 2013/07/19 06:00
MHDA- 2014/03/19 06:00
CRDT- 2013/07/18 06:00
PHST- 2013/07/18 06:00 [entrez]
PHST- 2013/07/19 06:00 [pubmed]
PHST- 2014/03/19 06:00 [medline]
AID - 10.2217/pgs.13.111 [doi]
PST - ppublish
SO  - Pharmacogenomics. 2013 Jul;14(10):1167-78. doi: 10.2217/pgs.13.111.