Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid
Background: Blood-cerebrospinal fluid (CSF) barrier transporters affect the influx and efflux of drugs. The antiretrovirals tenofovir and emtricitabine may be substrates of blood-brain barrier (BBB) and blood-CSF barrier transporters, but data are limited regarding the pharmacogenetics and pharmacok...
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doaj-7f85d4fa82924e2aa5b4c4178b64f9e32021-05-10T13:21:31ZengAOSISSouthern African Journal of HIV Medicine1608-96932078-67512021-04-01221e1e2410.4102/sajhivmed.v22i1.1206747Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluidEric H. Decloedt0Phumla Z. Sinxadi1Lubbe Wiesner2John A. Joska3David W. Haas4Gary Maartens5Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town; Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape TownDivision of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape TownDivision of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape TownDepartment of Psychiatry and Mental Health, Health Sciences, Groote Schuur Hospital, University of Cape Town, Cape TownDepartment of Medicine, Vanderbilt University Medical Center, Vanderbilt University, Nashville, Tennessee; Department of Internal Medicine, Meharry Medical College, Nashville, TennesseeDivision of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape TownBackground: Blood-cerebrospinal fluid (CSF) barrier transporters affect the influx and efflux of drugs. The antiretrovirals tenofovir and emtricitabine may be substrates of blood-brain barrier (BBB) and blood-CSF barrier transporters, but data are limited regarding the pharmacogenetics and pharmacokinetics of their central nervous system (CNS) penetration. Objectives: We investigated genetic polymorphisms associated with CSF disposition of tenofovir and emtricitabine. Method: We collected paired plasma and CSF samples from 47 HIV-positive black South African adults who were virologically suppressed on efavirenz, tenofovir and emtricitabine. We considered 1846 single-nucleotide polymorphisms from seven relevant transporter genes (ABCC5, ABCG2, ABCB1, SLCO2B1, SCLO1A2, SLCO1B1 and ABCC4) and 782 met a linkage disequilibrium (LD)-pruning threshold. Results: The geometric mean (95% confidence interval [CI]) values for tenofovir and emtricitabine CSF-to-plasma concentration ratios were 0.023 (0.021–0.026) and 0.528 (0.460–0.605), respectively. In linear regression models, the lowest p-value for association with the tenofovir CSF-to-plasma ratio was ABCB1 rs1989830 (p = 1.2 × 10−3) and for emtricitabine, it was ABCC5 rs11921035 (p = 1.4 × 10−3). None withstood correction for multiple testing. Conclusion: No genetic polymorphisms were associated with plasma, CSF concentrations or CSF-to-plasma ratios for either tenofovir or emtricitabine.https://sajhivmed.org.za/index.php/hivmed/article/view/1206pharmacokineticspharmacogeneticstenofoviremtricitabinecerebrospinal fluid |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eric H. Decloedt Phumla Z. Sinxadi Lubbe Wiesner John A. Joska David W. Haas Gary Maartens |
spellingShingle |
Eric H. Decloedt Phumla Z. Sinxadi Lubbe Wiesner John A. Joska David W. Haas Gary Maartens Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid Southern African Journal of HIV Medicine pharmacokinetics pharmacogenetics tenofovir emtricitabine cerebrospinal fluid |
author_facet |
Eric H. Decloedt Phumla Z. Sinxadi Lubbe Wiesner John A. Joska David W. Haas Gary Maartens |
author_sort |
Eric H. Decloedt |
title |
Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid |
title_short |
Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid |
title_full |
Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid |
title_fullStr |
Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid |
title_full_unstemmed |
Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid |
title_sort |
pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid |
publisher |
AOSIS |
series |
Southern African Journal of HIV Medicine |
issn |
1608-9693 2078-6751 |
publishDate |
2021-04-01 |
description |
Background: Blood-cerebrospinal fluid (CSF) barrier transporters affect the influx and efflux of drugs. The antiretrovirals tenofovir and emtricitabine may be substrates of blood-brain barrier (BBB) and blood-CSF barrier transporters, but data are limited regarding the pharmacogenetics and pharmacokinetics of their central nervous system (CNS) penetration.
Objectives: We investigated genetic polymorphisms associated with CSF disposition of tenofovir and emtricitabine.
Method: We collected paired plasma and CSF samples from 47 HIV-positive black South African adults who were virologically suppressed on efavirenz, tenofovir and emtricitabine. We considered 1846 single-nucleotide polymorphisms from seven relevant transporter genes (ABCC5, ABCG2, ABCB1, SLCO2B1, SCLO1A2, SLCO1B1 and ABCC4) and 782 met a linkage disequilibrium (LD)-pruning threshold.
Results: The geometric mean (95% confidence interval [CI]) values for tenofovir and emtricitabine CSF-to-plasma concentration ratios were 0.023 (0.021–0.026) and 0.528 (0.460–0.605), respectively. In linear regression models, the lowest p-value for association with the tenofovir CSF-to-plasma ratio was ABCB1 rs1989830 (p = 1.2 × 10−3) and for emtricitabine, it was ABCC5 rs11921035 (p = 1.4 × 10−3). None withstood correction for multiple testing.
Conclusion: No genetic polymorphisms were associated with plasma, CSF concentrations or CSF-to-plasma ratios for either tenofovir or emtricitabine. |
topic |
pharmacokinetics pharmacogenetics tenofovir emtricitabine cerebrospinal fluid |
url |
https://sajhivmed.org.za/index.php/hivmed/article/view/1206 |
work_keys_str_mv |
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