Clinical pharmacology of tenofovir clearance: a pharmacokinetic/pharmacogenetic study on plasma and urines.
Pharmacogenomics J
; 16(6): 514-518, 2016 11.
Article
em 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Membrana Transportadoras
/
Farmacogenética
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Inibidores da Transcriptase Reversa
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Fármacos Anti-HIV
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Polimorfismo de Nucleotídeo Único
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Proteínas Associadas à Resistência a Múltiplos Medicamentos
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Tenofovir
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Variantes Farmacogenômicos
Tipo de estudo:
Etiology_studies
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Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
Pharmacogenomics J
Ano de publicação:
2016
Tipo de documento:
Article