Factors associated with daily tenofovir exposure in Thai subjects taking combination antiretroviral therapy

© Copyright 2015, Mary Ann Liebert, Inc. 2015. Tenofovir (TFV) exposure is associated with antiretroviral efficacy and risk of kidney disease. There is evidence of high interindividual variability of the pharmacokinetics of TFV. The effect of several clinical conditions on the pharmacokinetics of TF...

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Main Authors: Stephen J. Kerr, Baralee Punyawudho, Narukjaporn Thammajaruk, Angela Colbers, Prachya Chaiyahong, Supalak Phonphithak, Vorapot Sapsirisavat, Kiat Ruxrungtham, David M. Burger, Anchalee Avihingsanon
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Published: 2018
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/44372
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spelling th-cmuir.6653943832-443722018-04-25T07:49:12Z Factors associated with daily tenofovir exposure in Thai subjects taking combination antiretroviral therapy Stephen J. Kerr Baralee Punyawudho Narukjaporn Thammajaruk Angela Colbers Prachya Chaiyahong Supalak Phonphithak Vorapot Sapsirisavat Kiat Ruxrungtham David M. Burger Anchalee Avihingsanon Agricultural and Biological Sciences © Copyright 2015, Mary Ann Liebert, Inc. 2015. Tenofovir (TFV) exposure is associated with antiretroviral efficacy and risk of kidney disease. There is evidence of high interindividual variability of the pharmacokinetics of TFV. The effect of several clinical conditions on the pharmacokinetics of TFV has been observed and may partly explain its variability. We assessed factors influencing the pharmacokinetics of TFV in Thai patients. Thirty participants (50% female) taking efavirenz- or ritonavir-boosted protease inhibitor-based regimens were investigated. Intensive pharmacokinetic sampling was performed over 24 h. Multivariate geometric mean regression models adjusted for covariates with p≤0.2 in univariate analysis were developed. The median age was 41 years. Five participants [three taking a protease inhibitor (PI) and two taking efavirenz (EFV)] had mild renal dysfunction [estimated glomerular filtration rate (eGFR) 60-90 ml/min/1.73 m 2 ; range 72-89]. TFV AUC 0-24 was 23% (95% CI 1-49%; p=0.04) higher in those taking PI vs. EFV, 39% (95% CI 5-84%; p=0.02) higher in those with mild renal dysfunction, and reduced by 16% (95% CI 5-26%; p=0.008) with each 10 kg body weight increase, after adjusting for sex and duration of TFV exposure. In PI-treated subjects TFV AUC 0-24 increased by 3% (0.3-6%; p=0.03) for each mg·h/liter increase in ritonavir (RTV) AUC 0-24 after adjusting for sex, weight, mild renal impairment, and proximal renal tubular dysfunction. Significantly higher TFV exposures were independently associated with PI regimens, mild renal impairment, lower body weight, and increasing RTV AUC 0-24 . Clinicians should be aware of the effect of these factors on TFV exposure when this drug is prescribed. 2018-01-24T04:41:41Z 2018-01-24T04:41:41Z 2015-04-01 Journal 19318405 08892229 2-s2.0-84951574879 10.1089/aid.2014.0249 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84951574879&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/44372
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Agricultural and Biological Sciences
spellingShingle Agricultural and Biological Sciences
Stephen J. Kerr
Baralee Punyawudho
Narukjaporn Thammajaruk
Angela Colbers
Prachya Chaiyahong
Supalak Phonphithak
Vorapot Sapsirisavat
Kiat Ruxrungtham
David M. Burger
Anchalee Avihingsanon
Factors associated with daily tenofovir exposure in Thai subjects taking combination antiretroviral therapy
description © Copyright 2015, Mary Ann Liebert, Inc. 2015. Tenofovir (TFV) exposure is associated with antiretroviral efficacy and risk of kidney disease. There is evidence of high interindividual variability of the pharmacokinetics of TFV. The effect of several clinical conditions on the pharmacokinetics of TFV has been observed and may partly explain its variability. We assessed factors influencing the pharmacokinetics of TFV in Thai patients. Thirty participants (50% female) taking efavirenz- or ritonavir-boosted protease inhibitor-based regimens were investigated. Intensive pharmacokinetic sampling was performed over 24 h. Multivariate geometric mean regression models adjusted for covariates with p≤0.2 in univariate analysis were developed. The median age was 41 years. Five participants [three taking a protease inhibitor (PI) and two taking efavirenz (EFV)] had mild renal dysfunction [estimated glomerular filtration rate (eGFR) 60-90 ml/min/1.73 m 2 ; range 72-89]. TFV AUC 0-24 was 23% (95% CI 1-49%; p=0.04) higher in those taking PI vs. EFV, 39% (95% CI 5-84%; p=0.02) higher in those with mild renal dysfunction, and reduced by 16% (95% CI 5-26%; p=0.008) with each 10 kg body weight increase, after adjusting for sex and duration of TFV exposure. In PI-treated subjects TFV AUC 0-24 increased by 3% (0.3-6%; p=0.03) for each mg·h/liter increase in ritonavir (RTV) AUC 0-24 after adjusting for sex, weight, mild renal impairment, and proximal renal tubular dysfunction. Significantly higher TFV exposures were independently associated with PI regimens, mild renal impairment, lower body weight, and increasing RTV AUC 0-24 . Clinicians should be aware of the effect of these factors on TFV exposure when this drug is prescribed.
format Journal
author Stephen J. Kerr
Baralee Punyawudho
Narukjaporn Thammajaruk
Angela Colbers
Prachya Chaiyahong
Supalak Phonphithak
Vorapot Sapsirisavat
Kiat Ruxrungtham
David M. Burger
Anchalee Avihingsanon
author_facet Stephen J. Kerr
Baralee Punyawudho
Narukjaporn Thammajaruk
Angela Colbers
Prachya Chaiyahong
Supalak Phonphithak
Vorapot Sapsirisavat
Kiat Ruxrungtham
David M. Burger
Anchalee Avihingsanon
author_sort Stephen J. Kerr
title Factors associated with daily tenofovir exposure in Thai subjects taking combination antiretroviral therapy
title_short Factors associated with daily tenofovir exposure in Thai subjects taking combination antiretroviral therapy
title_full Factors associated with daily tenofovir exposure in Thai subjects taking combination antiretroviral therapy
title_fullStr Factors associated with daily tenofovir exposure in Thai subjects taking combination antiretroviral therapy
title_full_unstemmed Factors associated with daily tenofovir exposure in Thai subjects taking combination antiretroviral therapy
title_sort factors associated with daily tenofovir exposure in thai subjects taking combination antiretroviral therapy
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84951574879&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/44372
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