Clinical pharmacology of tenofovir clearance: a pharmacokinetic/pharmacogenetic study on plasma and urines.
Pharmacogenomics J
; 16(6): 514-518, 2016 11.
Article
in En
| MEDLINE
| ID: mdl-26440731
ABSTRACT
The HIV virus and hepatitis B virus nucleotide reverse transcriptase inhibitor tenofovir has been associated with proximal tubular toxicity; the latter was found to be predicted by plasma concentrations and with single-nucleotide polymorphisms in transporters-encoding genes. A cross-sectional analysis in adult HIV-positive patients with estimated creatinine clearance >60 ml min-1 was performed. Twelve-hour plasma and urinary tenofovir concentrations and single-nucleotide polymorphisms in several transporter-encoding genes were analysed. In 289 patients 12-h tenofovir plasma, urinary and urinary to plasma ratios were 69 ng ml-1 (interquartile range 51.5-95), 24.3 mg ml-1 (14.3-37.7) and 384 (209-560). At multivariate analysis estimated creatinine clearance, protease inhibitors co-administration and SLC28A2 CT/TT genotypes were independently associated with plasma tenofovir exposure; ABCC10 GA/AA genotypes and protease inhibitor co-administration were independently associated with the urinary to plasma tenofovir ratio. Tenofovir clearance was associated with genetic polymorphisms in host genes and with co-administered drugs if confirmed by ongoing studies these data may inform treatment tailoring and/or dose reductions.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Membrane Transport Proteins
/
Pharmacogenetics
/
Reverse Transcriptase Inhibitors
/
Anti-HIV Agents
/
Polymorphism, Single Nucleotide
/
Multidrug Resistance-Associated Proteins
/
Tenofovir
/
Pharmacogenomic Variants
Type of study:
Etiology_studies
/
Observational_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Language:
En
Journal:
Pharmacogenomics J
Year:
2016
Document type:
Article