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.The Pharmacogenomics Journal advance online publication, 6 October 2015; doi:10.1038/tpj.2015.71.

Clinical pharmacology of tenofovir clearance: a pharmacokinetic/pharmacogenetic study on plasma and urines

CALCAGNO, Andrea
First
;
CUSATO, JESSICA;MARINARO, Letizia;TRENTINI, Laura;ALCANTARINI, Chiara;SIMIELE, MARCO;D'AVOLIO, ANTONIO;DI PERRI, Giovanni;BONORA, Stefano
Last
2016

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.The Pharmacogenomics Journal advance online publication, 6 October 2015; doi:10.1038/tpj.2015.71.
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Calcagno, A; Cusato, J; Marinaro, L; Trentini, L; Alcantarini, C; Mussa, M; Simiele, M; D'Avolio, A; Di Perri, G; Bonora, S
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1618847
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